06.06.2024

The f-ORG technique will detect the smallest changes in human photoreceptors – new paper in Optics Letters

Photoreceptors are the fundamental component of the entire vision process. These specialized cells that absorb light and trigger a specific physiological reaction in the body come in two varieties: cones (responsible for sharp color vision) and rods (responsible for black-and-white vision in low light, e.g. after dark). To properly receive visual stimuli and perceive the world around us, we need both in large quantities.

Flicker electroretinography (f-ERG) is a valuable tool that has been used for decades to study the physiological functions of the retina. Scientists from the International Centre for Translational Eye Research – ICTER, operating within the Institute of Physical Chemistry, Polish Academy of Sciences, have made great progress in developing a technique that is its optical equivalent – flicker optoretinography (f-ORG) – which may be applied in diagnosing certain visual disorders.

A team of scientists consisting of Sławomir Tomczewski, Piotr Węgrzyn, Maciej Wojtkowski and Andrea Curatolo developed a method that allows for quick measurement of the frequency characteristics of photoreceptors’ response to flicker stimulation. The work “Chirped flicker optoretinography for in vivo characterization of human photoreceptors’ frequency response to light” was published in the journal Optics Letters.

Optoretinography is a step ahead of electroretinography

Many eye diseases have a complex structure-function relationship, and photoreceptor abnormalities often manifest themselves on various levels, including their appearance and operation. The time interval between functional deficits and the perceived pathological changes in the eye is variable and difficult to determine, and in ophthalmological practice, psychophysical methods (e.g. microperimetry, tests of sensitivity to flickering light) and electrophysical methods (e.g. electroretinography) are used.

Electroretinography (ERG) is an objective, slightly invasive method capable of measuring electrical potentials from retinal neurons in response to light stimulation. This technique has proven effective in the early detection of retinitis pigmentosa, X-linked retinal detachment, and diabetic retinopathy. In recent years, it has been shown that optical coherence tomography (OCT) allows the detection of small changes in the structure of the retina occurring in response to a light stimulus. This was the basis for developing optoretinography (ORG) – the optical and non-invasive equivalent of ERG.

Professor Maciej Wojtkowski’s team focuses on the use of flickering light to stimulate the retina (f-ORG method). In 2022, in their previous publication on f-ORG, the ICTER team showed that it is possible to perform f-ORG measurements in a largefrequency range (up to 50 Hz). In their latest work, the ICTER research team proposed a new approach to f-ORG measurements allowing for quick determination of the frequency characteristics of photoreceptors.

“A flicker protocol with variable instantaneous frequency combined with appropriate light adaptation has two advantages. On the one hand, it enables rapid measurement of the frequency response characteristics of photoreceptors; on the other hand, it also allows you to shorten the time between measurements by avoiding several minutes of adaptation to darkness.” – says Dr. Sławomir Tomczewski from ICTER.

Important findings regarding f-ORG

In the standard f-ORG approach, obtaining a full frequency response of the human eye’s photoreceptors to flicker requires a large number of measurements at separate stimulus frequencies and time-consuming data processing for each of these sets.

Implementing variable frequency flicker into f-ORG significantly decreases the number of measurements needed to characterize the frequency response of photoreceptors, drastically reducing the time required to conduct experiments and analyze data. ICTER scientists have shown that there are no significant differences between results obtained using this new, fast approach and a separatefrequency flicker ORG.

Taking into account the limited number of objects and measurements, the research carried out is preliminary and requires further development. Work is currently underway to explain the mechanism of the phenomenon used in ORG and its relationship with the vision process. Ultimately, the new tool developed at ICTER may deliver a new frequency response-based biomarker for early detection of retinal diseases and therapy monitoring.

Author of the press note: Marcin Powęska.

Related paper:

“Chirped flicker optoretinography for in vivo characterization of human photoreceptors’ frequency response to light” authors: Dr. Sławomir Tomczewski; Piotr Węgrzyn, Prof. Maciej Wojtkowski and Dr. Andrea Curatolo. Journal: Optics Letters. Vol. 49, Issue 9, pp. 2461-2464 (2024). DOI: https://doi.org/10.1364/OL.514637.

Image: Piotr Węgrzyn & DALL-E.

20.05.2024

ICTER at the Ursynów Science Festival in Warsaw on May 23 – invitation to optical and eye model design workshops

We kindly invite the public to visit our stands and participate in the workshops that we have prepared for young people and adults at the Ursynów Science Festival in Warsaw this Thursday. Please see below for details.

📅 Date: Thursday, May 23, 2024
🕒 Time: 12:00-18:00
📍 Location: Ursynów Cultural Center “Alternatywy”, 9 Indira Gandhi Street, Warsaw, Poland
🚇 Public transport by metro: M1, Imielin stop
🎫 Free admission, youth and adults welcome

𝗠𝗮𝗶𝗻 𝗵𝗮𝗹𝗹, first floor of Ursynów Cultural Center “Alternatywy”

𝗜𝘀𝗮𝗱𝗼𝗿𝗮 𝗜𝗜 Room:
Workshop – Designing the eye model
12:15-12:45 p.m.
13:00-13:30

Workshop – Optical illusions
14:00-14:30 hrs.
14:45-15:15 hrs

𝗠𝗮𝘁𝗲𝗷𝗸𝗼 Room:
Optical workshop
17:00-17:30

𝗣𝗮𝗿𝗸𝗶𝗻𝗴 at Ursynów Cultural Center “Alternatywy”

Stand/Workshop:
Sight – the most important of the senses:

  • Visual acuity test, vision test
  • Poster on retinal diseases and OCT method
  • Information on research being developed at ICTER
  • Stereoscopic and color vision

The idea of the festival is to popularize science among young, but also older residents of Ursynów and Warsaw. The festival is organized by LXIII Lajos Kossuth High School in Warsaw together with the Ursynów District of the City of Warsaw.

More information and schedule of the event: https://ursynow.um.warszawa.pl/-/ursynowski-festiwal-nauki-3.

We look forward to welcoming the public to this activity.

24.04.2024

European Funds Open Days at ICTER – we invite you to an educational workshop for youth and adults “Sight – the most important of the senses” on May 10, 2024

The full description of the event is available in Polish below.

Międzynarodowe Centrum Badań Oka – ICTER, działające w ramach Instytutu Chemii Fizycznej Polskiej Akademii Nauk, jest ośrodkiem naukowo-badawczym stworzonym w celu rozwinięcia nowoczesnych technologii wspierających diagnostykę i terapię chorób oczu, pozwalających na szybsze wdrożenie nowych terapii. Naukowcy z ICTER współpracują z prestiżowymi ośrodkami okulistycznymi w Europie i Ameryce Północnej: Institute of Ophthalmology w University College London, oraz Gavin Herbert Eye Institute na Uniwersytecie Kalifornijskim w Irvine.

Projekt „Międzynarodowe Centrum Badań Oka” jest realizowany w ramach działania MAB FENG 02.01. Fundacji na rzecz Nauki Polskiej współfinansowanego przez Unię Europejską z Europejskiego Funduszu Rozwoju Regionalnego, z Funduszy Europejskich dla Nowoczesnej Gospodarki, nr umowy FENG.02.01-IP.05-T005/23.

W ramach obchodów 20-lecia Polski w UE, w 2024 roku ICTER bierze udział w akcji Dni Otwarte Funduszy Europejskich. Oferujemy Państwu udział w edukacyjnych warsztatach dla młodzieży i dorosłych: „Wzrok – najważniejszy ze zmysłów” w siedzibie ICTER przy ul. Skierniewickiej 10A (parter) w dzielnicy Wola w Warszawie (01-230), w piątek 10 maja, o godzinie 11:00 lub 13:00 (do wyboru przy rejestracji).

Poniżej przedstawiamy plan warsztatów:

1. Oglądanie przygotowanych elementów biologicznych w powiększeniu przy użyciu mikroskopu świetlnego.

2. Ocena siatkówki oka przy użyciu optycznej koherentnej tomografii (OCT). Wykonanie pomiaru* za pomocą komercyjnego urządzenia OCT Revo firmy Optopol. 

*Konieczna jest podpisana zgoda na badanie przez uczestnika bądź prawnego opiekuna osoby biorącej udział w wydarzeniu. 

Optyczna Koherentna Tomografia (OCT) to nieinwazyjna, bezdotykowa metoda wykorzystywana w obrazowaniu struktury siatkówki oka ludzkiego w wysokiej rozdzielczości. Metoda ta wykorzystuje wiązkę światła, którą skanowana jest siatkówka oka, a następnie analizowany jest współczynnik odbicia światła od poszczególnych warstw siatkówki. Badanie OCT umożliwia ocenę grubości siatkówki oraz diagnostykę chorób narządu wzroku. 

Grupa 1 (maks. 20 osób):

11.00 – 11.15 – przywitanie gości oraz prezentacja

11.15 – 11.50 – warsztat grupa 1

zwiedzanie laboratoriów grupa 2

11.55 – 12.30 – warsztat grupa 2

zwiedzanie laboratoriów grupa 1

Grupa 2 (maks. 20 osób):

13.00 – 13.15 – przywitanie gości oraz prezentacja

13.15 – 13.50 – warsztat grupa 3

zwiedzanie laboratoriów grupa 4

13.55 – 14.30 – warsztat grupa 4

zwiedzanie laboratoriów grupa 3

Rejestracja w warsztatach:

W celu wzięcia udziału w warsztatach, wymagana jest uprzednia rejestracja. Formularz rejestracyjny dostępny jest pod linkiem: https://forms.office.com/e/D4tHE7vtBN. Zapisy przyjmujemy do 7 maja 2024 r. włącznie.

Regulamin wydarzenia oraz klauzule RODO:

Prosimy o zapoznanie się z Planem, Regulaminem, jak również klauzulami RODO dot. wydarzenia pod linkiem: https://icter.pl/pl/plan-i-regulamin-uczestnictwa-w-edukacyjnych-warsztatach-dla-mlodziezy-i-doroslych-wzrok-najwazniejszy-ze-zmyslow-w-icter-ichf-pan-2/.

Udział młodzieży w warsztatach, wymagana zgoda:

Oprócz dorosłych serdecznie zapraszamy również młodzież (powyżej 12 roku życia) do uczestnictwa w naszych warsztatach edukacyjnych. Udział w Warsztatach osób, które nie ukończyły 18 roku życia, wymaga dostarczenia oryginału zgody rodzica lub opiekuna prawnego do ICTER na ul. Skierniewicką 10A (parter) w Warszawie (01-230) w dniu warsztatów.

Formularz zgody znajduje się pod linkiem: https://icter.pl/pl/zgoda-rodzica-lub-opiekuna-prawnego-na-udzial-dziecka-w-edukacyjnych-warsztatach-dla-mlodziezy-i-doroslych-wzrok-najwazniejszy-ze-zmyslow-w-siedzibie-icter-2/.

Pomiar OCT, wymagana zgoda:

Jedną z atrakcji, które oferujemy w ramach edukacyjnych warsztatów dla młodzieży i dorosłych „Wzrok najważniejszy ze zmysłów” w siedzibie ICTER jest ocena siatkówki oka przy użyciu optycznej koherentnej tomografii (OCT) poprzez wykonanie pomiaru za pomocą komercyjnego urządzenia OCT Revo firmy Optopol. W celu wzięcia udziału w pomiarze konieczna jest podpisana zgoda na badanie przez uczestnika bądź prawnego opiekuna osoby biorącej udział w wydarzeniu. Poniżej znajduje się link do treści formularza zgody, jak również do informacji dot. RODO związanych z pomiarem.

ZGODA NA POMIAR OCT REVO: https://icter.pl/wp-content/uploads/2024/04/Zgoda-na-pomiar-OCT-Revo-w-ICTER.pdf.

INFORMACJE RODO DOT. POMIARU OCT REVO: https://icter.pl/wp-content/uploads/2024/04/RODO-Badania-OCT-Revo.pdf.

W przypadku uczestników małoletnich (powyżej 12 roku życia) prosimy o wydrukowanie, podpisanie formularza przez rodzica lub opiekuna prawnego dziecka i dostarczenie go na warsztaty w dniu wydarzenia do ICTER na ul. Skierniewicką 10A (parter) w Warszawie (01-230).

Uczestnicy pełnoletni mają możliwość podpisania formularza w dniu warsztatów, przed przystąpieniem do pomiaru OCT.

Obchody 20-lecia Polski w UE:

Zapraszamy do odwiedzenia strony 20lat.eu, gdzie widnieją nasze edukacyjne warsztaty dla młodzieży i dorosłych „Wzrok najważniejszy ze zmysłów” oraz inne wydarzenia w ramach Dni Otwartych Funduszy Europejskich: Dwudziestolecie Polski w Unii Europejskiej (20lat.eu).

02.04.2024

Stargardt’s disease has many names. Different varieties require different approaches – research from ICTER published in PNAS Journal

Stargardt’s disease is a rare eye condition that affects both children and adults, in many cases leading to blindness. It has several different varieties, and new research indicates that each requires a slightly different therapeutic approach. This key discovery may contribute to the development of effective methods to combat this currently incurable disease.

Initially, patients experience a sudden loss of sharp and central vision. The disorders progress, often making normal functioning difficult, including reading or face recognition. For many people, just looking at a light source is painful. After some time, the disease may stabilize, but often the damage to the macula is so significant that vision loss occurs.

The above description concerns Stargardt’s disease, a disorder that affects approximately 1 in 10,000 people, most often children between 8 and 12 years of age. There is no cure for this macular dystrophy, but understanding the mechanisms that occur in photoreceptors during the disease is crucial for potential therapeutic interventions (several drugs are being tested). It turns out that different types of Stargardt’s disease – although they have a similar cause – respond differently to different classes of drugs.

Research conducted with the participation of scientists from the International Centre for Translational Eye Research (ICTER) at the Institute of Physical Chemistry, Polish Academy of Sciences, including Dr. Marcin Tabaka, Dr. Andrzej Foik, Dr. Damian Panas, Dr. Jagoda Płaczkiewicz, and Dr. Katarzyna Kordecka, in cooperation with the Center for Translational Vision Research at the Gavin Herbert Eye Institute (CTVR) from UC Irvine in California under the supervision of Prof. Krzysztof Palczewski, resulted in a paper published in PNAS entitled “Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses”, which increases our understanding of Stargardt’s disease.

Stargardt’s disease is not just one disease

Lipids are an important component of the biological activity and physiology of most cells in the body, and in particular, they play a key role in the functioning of the retina. It has been confirmed that disturbed lipid homeostasis occurs in various degenerative retinal diseases, although still little is known about lipid profiles in normal and diseased retinas.

Stargardt’s disease is characterized by the accumulation of a non-degradable derivative of the visual pigment – lipofuscin – in the retinal pigment epithelium (RPE), which causes its atrophy. From the first description of Stargardt’s disease until recently, its diagnosis was based on the evaluation of the phenotype by eye examination, but since the advent of genetic testing, the picture of the condition has become more complete.

What was originally thought to be one disease is probably at least three variants (STGD1, STGD4, STGD3), each associated with a different genetic change. Therefore, it is extremely difficult to clearly define what Stargardt’s disease is, let alone think about potential treatments.

The most common form of Stargardt disease – STGD1 – is caused by biallelic variants of the Abca4 gene (i.e. autosomal recessive), and their exact genotype (i.e. combinations of both variants) is of great prognostic importance as to the age of disease onset and its progression. The frequency of Abca4 allele carriers in the general population is 5-10%, and different gene combinations influence the age of onset and the severity of the disease itself. Furthermore, disease severity is inversely related to ABCA4 function, and mutations in this gene are thought to play a role in other diseases such as retinitis pigmentosa, rod and cone dystrophies, and Age-Related Macular Degeneration (AMD). Macular Degeneration).

Biochemistry of Stargardt’s disease

Two genes encoding lipid-processing proteins have been associated with inherited retinal degenerative diseases. Mutations in the gene encoding an enzyme called ELOVL4 elongase, involved in building long-chain fatty acids, have been associated with autosomal dominant AMD-like Stargardt disease – STDG3 variant. Patients suffering from this disease at a young age experience loss of central vision. In turn, the disease in people suffering from STGD4 has been associated with mutations in the Prom1 gene. This disease variant was discovered in 1999 and little is known about its cause, except that there is a mutation at the p.R373C site, which causes dystrophy of cones and rods.

However, the most common form of Stargardt disease – STDG1 – is quite well understood. Patients showed a progressive bilateral appearance of yellow-orange spots (lipofuscin) in the macula, where the density of cones is highest. Such changes cause atrophy of the RPE and the death of photoreceptors in this region, resulting in vision loss. Lipofuscin accumulation in the RPE is a characteristic finding in the eyes of STGD1 patients and the mouse model of Stargardt disease.

Previous studies have shown that ABCA4 is expressed in the photoreceptor outer segment disc (POS disc) and the plasma membrane of RPE cells. ABCA4 transports a retinal phospholipid compound known as N-retinylidene-phosphatidylethanolamine (N-ret-PE) upon photoexcitation, allowing its removal from receptor cells – similarly to RPE cells, where N-ret-PE is transferred to lysosomes or phagosomes. In people with Stargardt disease (STDG1), N-ret-PE accumulates in POS discs and leads to the formation of the precursor A2E bisretinoid (A2PE). Inside the RPE lysosomes, A2PE is converted into A2E – a compound that cannot be broken down by any enzymes in the body. A2E is believed to react with other lipids and convert to lipofuscin deposits.

According to the current knowledge, over 100 mutations affect ABCA4 functions and are associated with a wide spectrum of Stargardt disease phenotypes. The suggestion that mutations in different domains of ABCA4 may affect the RPE and photoreceptors differently is tempting, meaning that ABCA4 has slightly different functions in them. This, in turn, opens a window into the potential therapeutic mechanism associated with lipid-lowering drugs.

Therapeutic hopes

Although there is no cure for Stargardt’s disease, work is underway on several therapies aimed at limiting or completely stopping the progression of this disease. The team led by Prof. Palczewski at CTVR and ICTER decided to investigate two alternative mouse models of functional ABCA4 deficiency to model the heterogeneity of mutations in patients with Stargardt disease and to see whether a different therapeutic approach might be necessary to stabilize retinal health in each case.

Using a combination of molecular techniques, the researchers examined Abca4 knockout mice (knock-out) and mice with additional Abca4 (knock-in). The researchers compared the two strains to determine whether they exhibited differential responses to factors that affect cytokine signaling and/or ceramide metabolism, as changes in either of these pathways can exacerbate retinal degenerative phenotypes.

Abca4 knockout and Abca4PV/PV knockout mice showed different responses to a ceramide-lowering drug and an immunomodulatory drug. The two mouse models were found to have divergent levels of baseline cellular stress and signaling, which are exacerbated in the early stages of light-induced retinal degeneration. Most importantly, these side effects can be alleviated prophylactically with the use of an immunomodulatory drug, thus “slowing down” the course of Stargardt’s disease.

“We found varying degrees of response to maraviroc, a known immunomodulatory CCR5 antagonist, and to the ceramide-lowering agent AdipoRon, an agonist of ADIPOR1 and ADIPOR2 receptors. Our phenotypic comparison of two different mouse models with the Abca4 mutation sheds light on potential therapeutic options previously unexplored in the treatment of Stargardt’s disease and provides a substitute test for assessing the effectiveness of gene therapy” – says Dr. Marcin Tabaka, leader of the ICTER Computational Genomics Team.

It is worth mentioning that in an earlier study, also published in PNAS, entitled “Stress resilience-enhancing drugs preserve tissue structure and function in degenerating retina via phosphodiesterase inhibition”, molecules that activate biological mechanisms of stress resistance were examined. This, in turn, may result in the development of a new class of pharmaceuticals, the so-called drugs that increase stress resistance (SRED) with potentially wide clinical significance for combating pathological retinal changes, not only Stargardt’s disease. A major contribution to the research work was made by the ICTER Computational Genomics Team, which analyzed single-cell sequencing data, enabling the identification of universal molecular mechanisms involved in age-related eye diseases and hereditary retinal degenerations.

The latest study makes a case for using transgenic knock-in mouse lines that have mutations analogous to those in humans. It also serves as a precursor to adopting these models to test genome editing methods that can precisely correct genetic mutations. Thanks to these efforts, Stargardt’s disease, which is today considered “incurable”, may become a disease that can be controlled and, as a result, save eyesight.

Author of the press release: Marcin Powęska.
Image: Deposit Photos.

Cited papers:
https://doi.org/10.1073/pnas.2314698120
https://doi.org/10.1073/pnas.2221045120

01.03.2024

ICTER is a laureate of the “The International Research Agendas” competition financed by the European Funds for Smart Economy Programme

On February 29, 2024 the Foundation for Polish Science (FNP) announced that ICTER is among the winners of the first two calls for proposals in the “International Research Agendas” (IRAP) activity funded by the European Funds for Smart Economy Programme (FENG).

The IRAP FENG activity supports the establishment or development of specialized, world-leading research teams and organizations where scientific excellence and international research competitiveness can be achieved (source: FNP).

The focus of our research program, supported by this grant, is to contribute to advancements in the field of medical science. Specifically, we aim to develop new tools for safer and more effective surgical interventions, pioneer groundbreaking therapies for eye diseases, and create diagnostic methods that enhance prognosis and restore vision.

We extend our gratitude to the ICTER team, the Institute of Physical Chemistry, Polish Academy of Sciences, the International Scientific Committee, our partners, and collaborators, for their contributions to this achievement.

We look forward to leveraging this opportunity to further advance scientific excellence and international competitiveness in our eye research initiatives.

Photo: Karol Karnowski, PhD.

The „International Centre for Translational Eye Research” project is carried out within the MAB FENG action 02.01.of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund, European Funds for Smart Economy, agreement no. FENG.02.01-IP.05-T005/23.

28.12.2023

“Inventing a technology is one thing but putting it into practice is quite another. ICTER allows both worlds to meet,” an interview with Dr. Bartosz Sikorski, an ophthalmologist and long-time ICTER collaborator

Dr. Bartosz Sikorski’s 20-year friendship with Prof. Maciej Wojtkowski resulted in several joint projects and patents that today facilitate the diagnosis of eye diseases worldwide. Without them, there would be no spectral OCT or OCT angiography, among others, which have changed the face of ophthalmology. But the exciting adventure continues! They are currently working together on two-photon vision, optoretinography (functional examination of the retina), and STOC (Spatio-Temporal OCT), which open up entirely new horizons.

How can modern ophthalmology be improved with new diagnostic methods? What does this mean for patients and, more broadly, for the whole of the society? You will learn about this from our interview with Dr. Bartosz Sikorski, an ophthalmologist, vitreoretinal surgeon and long-standing ICTER collaborator, a clinical expert in the field of eye imaging.

Interview with Dr. Bartosz Sikorski, an ophthalmologist and long-time ICTER collaborator


––––––––––––––––––––––––––––––

Bartosz L. Sikorski, MD, PhD graduated in medicine from NCU. He also studied at ICL, University of Oxford, and Harvard University. He is a Fellow of the European Board of Ophthalmology (Paris) and a Member of the Optical Biomedical Imaging Team at the Institute of Physics, NCU, which developed and commercialized Spectral-Domain OCT technology. Dr. Sikorski is the Medical Director of the AI detection project for retinal diseases.

Maciej Wojtkowski, PhD graduated in physics at NCU, where he then headed the Optical Biomedical Imaging Team. Professor Wojtkowski also worked at the University of Vienna and MIT. He and his co-workers developed the first Spectral-Domain OCT laboratory set-ups and clinical prototypes, and co-commercialized the technology. He is currently Chair of ICTER and the Physical Optics and Biophotonics Group at the Institute of Physical Chemistry, Polish Academy of Sciences in Warsaw.

Anna Przybyło-Józefowicz, PhD is responsible for fine-tuning and implementing the internal and external communication strategy for ICTER. She has 18 years of experience in the public and private sector, where she developed as a diplomat, manager, consultant, translator, writer, and university lecturer. She interviewed Dr. Bartosz Sikorski.

Karol Karnowski, PhD graduated in physics (MSc) and biophysics (PhD) at NCUr. From 2015 to 2018, he held a postdoctoral fellowship at the University of Western Australia, where he still holds the honorary position of Adjunct Senior Lecturer. Since 2018, he has led a project group working on the use of polarization contrast and miniature imaging probes. In addition, he led the group responsible for the design of a clinical prototype for multi-spot assessment of corneal biomechanics. At ICTER he is a senior researcher actively involved in research activities of IDoc and POB groups and supports the centre as PR photographer. He recorded and edited the video.

Marcin Powęska, MSc is a biologist, popular science journalist, author of numerous medical publications, and ICTER’s research editor. He crafted the title and social media material for this interview.

The International Centre for Translational Eye Research (www.icter.pl) is a centre of excellence hosted by the Institute of Physical Chemistry, Polish Academy of Sciences (https://ichf.edu.pl/) and carried out within the International Research Agendas programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund.

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Creative Commons — Attribution 3.0 Unported — CC BY 3.0

Free Download / Stream: https://bit.ly/3iH8rlX

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13.12.2023

“Optoretinography is the future of ophthalmology, and the knowledge from ICTER is utilized by top specialists” – interview with Prof. Robert Zawadzki from UC Davis

Thanks to medical progress, we can cure more and more vision-related diseases and the bottleneck of successful ophthalmological interventions is diagnostics. The stage at which changes in the retina are detected directly translates into the patient’s chances of recovery. One of the most innovative and fastest-growing ophthalmological techniques is optoretinography (ORG), the leader of which in Poland is Prof. Maciej Wojtkowski from ICTER. Many centers around the world research ORG, and many use the treasure trove of knowledge of ICTER scientists.

One of the most important research centers specializing in ORG in the United States is the University of California at Davis (UC Davis), where Prof. Robert Zawadzki – a graduate of the Nicolaus Copernicus University in Toruń and a long-time collaborator of ICTER – has worked for about 20 years. We asked him what he does at UC Davis; how his research can translate into patients’ health; what are his feelings after visiting ICTER and why cooperation between centers from all over the world is crucial for the future of ophthalmology.

Please tell us what project you are working on and with whom during your current visit to ICTER.

Yes, this is my follow-up visit to ICTER at the invitation of Prof. M. Wojtkowski. Our plan during my previous visit was to assist in two research projects. One involved setting up and testing a fundus camera, which was designed for the STOC-T system and is now used for functional eye imaging. This research was conducted in collaboration with Dr. Andrea Curatolo’s team, with Wiktor Kulesza and Piotr Węgrzyn. During that stay, we managed to obtain an image of the mouse eye fundus using the camera, which could be used to determine the precise location of the retina for subsequent functional measurements using STOC-T. The second project involved cooperation with Dr. Michał Dąbrowski, that focused on assisting in the two-photon fluorescence imaging of the retina. Here, I also helped Mr. Michał correct the image from the auxiliary single-photon scanning light ophthalmoscope system, for two-photon measurements. In both the STOC-T and two-photon projects, the primary scientific instruments did not have real-time high-quality images, and this is where assistance was needed to build systems that would help align the eyes during the examination. During my current stay, I also participated in the CRATER conference and then focused mainly on working with Dr. Andrea Curatolo’s team. We collaborated on a manuscript describing the STOC-T measurement system for mouse imaging and its applications. Additionally, we discussed issues related to finding permissible light exposure limits for STOC-T measurements on experimental animals, as well as the details of the STOC-T optical system and the potential impact of various components on the measurement system’s resolution.

This is not the first time you have come to our centre. Please tell us briefly about what has been achieved during your previous visits and in what direction further cooperation with ICTER researchers is going.

Indeed, these visits are a continuation of my previous ones. I have previously collaborated with the same teams. During one of my first visits, taking place over two years ago, Dr. Michał Dąbrowski was still building his system, so our collaboration was limited to assisting in selecting certain optical components, which were needed for the experiments we conducted in 2022. In the case of Dr. Andrea Curatolo, during my first visits, we collaborated on the design, construction, and initial setup of the system. I hope that both projects will continue to develop and, in the case of Dr. Curatolo, allow for functional measurements at the retina in laboratory animals using STOC-T, and in the case of Dr. Dąbrowski, be useful for two-photon fluorescence measurements that may provide us with more information about diseases of photoreceptors and retinal pigment epithelium, cells containing majority of fluorescent molecules in the eye.

From the left: Piotr Węgrzyn, Prof. Robert Zawadzki, Wiktor Kulesza and Dr. Andrea Curatolo at ICTER’s lab.

What areas do you specialize in and what are the unique effects of this non-obvious combination in practice?

I specialize in the field of biomedical engineering or bio-photonics, specifically focusing on building and utilizing systems for functional measurements in the eye, particularly on the retina, in both humans and experimental animals. The outcomes of my work involve the development of new devices that enable the measurement of functional changes at the cellular level resulting from disease-related changes or age-related alterations. In the future, these methods may contribute to better diagnostics and the assessment of the effectiveness of gene or stem cell therapies in such cases.

Please tell us about your research and work at UC Davis.

I have been at UC Davis for about 20 years now, and currently, I’m a professor in the Department of Ophthalmology & Vision Science. I’m a member of two research groups there. One group is focused on testing and building clinical research devices; it’s called CHOIR, which stands for the Centre for Human Ophthalmic Imaging Research. The other research group I’m part of, EyePod Small Animal Ocular Imaging Laboratory, is involved in small animal ocular imaging. We design and create new devices for structural and functional eye measurements, mainly in mice and small experimental animals. The research we conduct aims to develop new methods that can be useful for both clinical doctors and scientists working on fundamental medical research, where new methods such as gene and stem cell therapy are being developed. We are one of the groups that helps other research teams test their innovations more effectively and identify potential issues faster while also aiding them in discovering new directions for the development of these various therapies.

How can you translate your research results into measurable and useful applications for patients?

Our research has the potential to be useful for patients in the following two scenarios. The first is the development of devices to enhance the diagnosis of eye diseases, improving these methods to the extent that even for individuals who do not yet exhibit any objective changes in their vision, it will be possible to determine whether there are any underlying changes. This is particularly crucial among individuals with genetic predispositions that put them at an increased risk. Knowing a person’s specific genetic defect can help tailor diagnostic methods to identify functional changes in certain cells, potentially allowing for prevention or at least a delay in the progression of the disease, given the current state of the medicine. In cases where these therapies are expensive, this is indeed a significant aspect. The second direction of our research is to confirm whether the methods used to treat patients are effective. In this scenario, if we find no changes, the doctor may choose another method that produces better results. This aspect is perhaps more tangible for patients. Of course, our research is also crucial in the implementation of new therapeutic methods as it accelerates the development of these therapies.

Please tell us how the optoretinography technology developed with ICTER is state-of-the-art, where in the world is it currently being developed, and what is your unique contribution to its development?

The technology of optoretinography, referred to as the method of measuring the functional response of the retina to light stimulation, has unique diagnostic potential and is, therefore one of a kind, it is currently being researched in various laboratories to understand how the signals measured using ORG can be linked to known physiological functions of individual retinal neurons. In Europe is primarily being developed by groups like ICTER led by Maciej Wojtkowski, a strong group in Germany under Geron Huettmann, and another group in Paris, lead by Kate Grieve. In United States, we have groups at UC Davis, University of Washington led by Ramkumar Sabesan, Indiana University led by Don Miller. There are also groups at the University of Illinois Chicago, the University of Wisconsin, the University of Pennsylvania and at Stanford University, just to name a few. All these groups focus on various aspects of ORG. My contribution to the development of this method involves e elucidating the physiological factors related to these signals. We have been able to confirm that changes in retinal water content are responsible for a portion of the signals we measure. This is a secondary effect following photoreceptor light activation but is related to water. Additionally, in our group, which develops devices for clinical research, we aim to create models that would enable us to validate our results, making it easier to determine the main characteristics of the optoretinography signal. Our research is directed towards finding better methods for optoretinographic measurements, discovering what truly influences the signal we measure. Note that we mainly measure changes in the thickness of certain retinal layers and alterations in light scattering. We are also developing methods to model these signals and more easily find correlations between the parameters of these curves and various eye diseases.

From the left: Dr. Michał Dąbrowski, Prof. Robert Zawadzki, and Bartłomiej Bałamut at ICTER’s lab.

Please specify how your career and approach to science have been influenced by the different locations and units where you have worked so far: undergraduate and graduate studies at UMK in Toruń, PhD in Vienna, and work at UC Davis.

My undergrad studies at Nicholaus Copernicus University (UMK) in Toruń were indeed essential for me to find myself where I am now, but, as in most cases, one’s career path and life journey are highly individual and challenging to replicate for others. They are often the result of certain coincidences and opportunities that have appeared on my path, some of which I was able to seize while others eluded me. However, my undergraduate studies at UMK were crucial in gaining fundamental knowledge in experimental physics and the use of computers in physics. They laid the foundation for my understanding of the scientific alphabet, so to speak. Then, during my master’s studies, I had the incredible fortune to start collaborating with Prof. Andrzej Kowalczyk, who, in the late 1990s, had a European Tempus grant for sending young students on various internships. In my case, I had the opportunity to intern at a university in Vienna, where I first encountered the method, I currently work on, Optical Coherence Tomography (OCT), and I also met one of its inventors, Prof. Adolf Fercher. After completing my master’s degree, I received an offer to pursue a Ph.D. in Vienna under Prof. Fercher, which is when I embarked on my doctoral studies. This experience allowed me to become proficient in both the OCT method and the field of biophotonics, as well as understand how to design devices for studying the eyes and other organs and how to apply data analysis methods. Therefore, my doctoral work was instrumental in building the knowledge needed for what I do now. After completing my Ph.D. in Vienna, I worked briefly as an assistant at UMK, and then, after about six months, I received a job offer at UC Davis as a Postdoc in John Werner Laboratory. It was there that I engaged in a significant project funded by the National Eye Institute, which involved building the world’s first system that combined adaptive optics with OCT. The knowledge I had gained during my doctoral studies, particularly in using OCT to study corneal shape and detect eye aberrations, proved to be ideal for this project, as I already had a foundation in ocular aberrations and understanding the function of the eye as an imaging element, as well as the basics of OCT. This experience in Vienna had also allowed me to become familiar with then up-and-coming detection technique known as Fourier Domain OCT. So, when I went to UC Davis, I had all the knowledge necessary to complete this project, which involved creating the first working adaptive optics OCT (AO-OCT) system, and we demonstrated the first images with cellular resolution on the retina. Throughout the years working at UC Davis, I maintained collaborations with groups in Toruń, led by Prof. Maciej Wojtkowski, and in Vienna. As these eye imaging methods evolved, we contributed to their development, primarily focusing on optical coherence tomography angiography, a method for non-invasively measuring blood flow in the eye. We also worked on methods that combined several different imaging techniques such as OCT with SLO, which are utilized by many modern systems for retinal eye imaging. About 12 years ago I began using these systems for measurements in experimental animals. This was made possible through collaboration between UC Davis Department of Ophthalmology (Prof. John Werner’s group) and the Department of Physiology, where Prof. Edward Pugh was involved. Through our collaboration with Ed Pugh, we created the EyePod team, which focused on studying the retina in experimental animals. It was around 2015 when we began working on ORG, or optoretinography. Thus, I continue to work in the same field, which I have been engaged in since my master’s studies, namely development and application of OCT in Medicine. I was able to do it by constantly applying the latest research method and technology. I have also been able to continuously expand my knowledge to keep my work as interesting and attractive as possible for these new emerging application fields.

What would you like to pass on to fellow scientists involved in eye research and the development of new ophthalmic therapies?

I would like to say that despite the fact that our new research methods and therapies seem very advanced, there are still many things we don’t know and cannot measure yet. I suspect that there is still a lot of work ahead of us to make these methods we are working on clinically available. Just as all these fields are still evolving, I would recommend young scientists to look at the current issues related to eye research. Perhaps even their individual experiences can be crucial in finding further solutions. So, the development of novel structural and functional assessment of the eye is something worth continuously engaging with.

Thank you very much for this interview, Prof. Robert Zawadzki. We eagerly anticipate further fruitful collaboration in the future.


Special thanks to all the ICTER scientists who participated in the photo session at our laboratories.

The interview was conducted by Dr. Anna Przybyło-Józefowicz (September 2023)

Title, introduction, and social media material: Journalist Marcin Powęska

Pictures: Dr. Karol Karnowski

05.12.2023

Exploring new horizons in eye research: CRATER 2023 Conference summary

CRATER 2023 is a unique event prepared by ICTER as a place to exchange ideas, disseminate research results, and explore the latest achievements related to the most important of our senses: vision.

Since 2019, scientists at the International Centre for Translational Eye Research (ICTER) have been working on breakthrough technologies for imaging and diagnosing eye diseases, facilitating procedures to save or restore vision. The research is interdisciplinary and covers biology, chemistry, physics, and computer science. A summary of the first period of ICTER’s activity was CRATER – Conference on Recent Advances in Translational Eye Research 2023 – which took place in the heart of Warsaw, at the Copernicus Science Center, on September 7-8, 2023. For the implementation of the event, a grant of PLN 320,000 was obtained under the “Excellent Science – Support for Scientific Conferences” program, financed by the Ministry of Education and Science. The event was co-organized by the Candela Foundation, whose statutory activity focuses on supporting the development of optics and photonics in Poland.

The conference aimed to bring together experts from various fields dealing with the process of vision in one place and enable them to exchange scientific ideas, as well as to create a bridge between the scientific world and industry. The conference focused on the latest achievements in the field of vision research, as well as new technologies and diagnostic tools, as well as methods of treating eye diseases. The range of topics covered was wide and included, among others: optogenetics, OCT optical tomography, two-photon imaging, structural biology, bioinformatics, electrophysiology, and the medical use of artificial intelligence (machine learning and deep learning).

Extraordinary guests and extraordinary conversations at CRATER 2023

Anna Clunes, British Ambassador to Poland, inaugurated the conference. During CRATER 2023, there were many interesting presentations in which experts from various specializations shared their knowledge. The conference was graced by the presence of such names as Pablo Artal, Chris Dainty, Francesca Fanelli, Arie Gruzman, Alison Hardcastle, Karl-Wilhelm Koch, Serge Picaud, and Olaf Strauss. Topics covered include the function of the retinal pigment epithelium (RPE), the possibility of restoring vision, the aging process of cells in the retinal vessels or the mechanisms of geographic atrophy (GA), the advanced stage of the dry form of age-related macular degeneration (AMD).

Parallel sessions covered, among others: the modeling of hereditary retinal diseases, processing of visual information, protection of light-sensitive cells (cones and rods), and the potential use of rhodopsin conformational modulators. All of these presentations offered a comprehensive overview of the latest developments in the field of vision research.

During CRATER 2023, prizes were awarded for the best-presented posters containing descriptions of scientific research. Lynn Kandakji, representing the UCL Institute of Ophthalmology, was honored for her poster titled “Subclinical Keratoconus Detection Using Deep Learning on Raw Anterior-Segment Optical Coherence Tomography Imaging.” Wiktor Kulesza from ICTER also received a distinction for his poster titled “Hemodynamics Monitoring in Mouse Retinal Vessels via Ultrafast Volumetric Spatio-Temporal Optical Coherence Tomography (STOC-T) Imaging”.

Success has many names

The conference provided a unique opportunity for those outside the eye research community to gain a concise and understandable overview of ICTER’s scientific achievements. Łukasz Kornaszewski, Deputy Director for Intellectual Property at ICTER, said:

Our industrial partners had the opportunity to see us in a natural environment. This event was an unusual and very effective way for non-specialists to understand the depth of our scientific achievements. We prepared informative and concise content, which made it accessible to a wider audience.

Looking at this event from yet another perspective and analyzing the impact of the CRATER conference through the lens of medicine, Piotr Chaniecki, Advisor to the ICTER Management Board for Ophthalmology, shared his observations:

This year’s CRATER conference was like a compass that showed the direction of development in global ophthalmology. Fascinating lectures and poster sessions showed how new technologies will help patients keep their eyes healthy. Soon, ophthalmologists will likely have powerful diagnostic and therapeutic tools at their disposal. For me, the great value lies in learning about technologies that will speed up the diagnosis of certain diseases, giving patients a chance to recover.

Maciej Wojtkowski, director of ICTER, emphasized the importance of the conference:

CRATER provided an important opportunity for ICTER to engage with the global eye research knowledge community. Thanks to the conference, we know where we are and where we are going. This exchange of knowledge allowed us to gain valuable experience and contacts that will bear fruit in the future.

Something more than an ordinary conference

The success of CRATER 2023 can also be measured in numbers. The event was attended by 168 people who represented a variety of environments and organizations. A survey conducted after the conference showed that participants were very satisfied with CRATER 2023. When asked to rate the conference, over 60% of respondents rated it a full 10 points out of 10.

CRATER 2023 was more than just an ordinary conference; was a celebration of the relentless pursuit of scientific and technological advancements in the field of vision research.

During the conference, two videos were recorded containing participants’ statements about the future of research and the event itself. These films undoubtedly reflect the atmosphere of the event. Links to videos below:

Summary: https://www.youtube.com/watch?v=5o2ekqTSF1U&ab_channel=IChFPAN.

Interviews: https://www.youtube.com/watch?v=4BvXBZTGrsY&ab_channel=IChFPAN.

Detailed information about CRATER can be found at: https://crater.icter.pl/.

Text: Anna Przybyło-Józefowicz and Marcin Powęska.

Content review: CRATER Organizing Comittee.