23.10.2024

Key to the invisible world found. ICTER scientists decipher two-photon vision

Two-photon vision is a novel method with great potential for the future of ophthalmic diagnostics. Although it has many advantages, it requires improvement in key areas. ICTER scientists have taken a step forward by improving this technology and opening up new perspectives in ocular medicine.

Imagine that instead of viewing an image through a lens, you look through a kaleidoscope that focuses invisible light to obtain a new range of colors. The photon, this ephemeral messenger of light, usually appears alone, but here it appears in a duet, which is the basis of two-photon vision. This extraordinary phenomenon in which the human eye, instead of perceiving traditional light, receives pulses of infrared lasers, the gateway to the invisible world.

However, the key to them is measuring the brightness of two-photon stimuli, which until now was only possible for visible light. ICTER scientists have made a breakthrough and determined the luminance value for infrared using photometric units (cd/m2). Thanks to this approach, it was possible to link the luminance of two-photon stimuli to a new physical quantity related to perceived brightness: the two-photon retinal illumination.

Research conducted by scientists from the International Centre for Eye Research (ICTER) with the participation of PhD student Oliwia Kaczkoś, PhD Eng. Katarzyna Komar and Prof. Maciej Wojtkowski have shown that the luminance of a two-photon stimulus can reach almost 670 cd/m2 in the safe range of laser power for the eye. The result is the paper entitled “Method for the determination of the luminance of two-photon vision stimuli,” published in the journal Biomedical Optics Express.

From left: Oliwia Kaczkoś and Dr. Katarzyna Komar. Photo by Dr. Karol Karnowski.

Seeing the Invisible World

The human eye can receive stimuli from the surrounding world in the form of electromagnetic waves in the range of about 380 nm to 780 nm (from violet to red). Waves outside this range, such as infrared (above 780 nm) and ultraviolet (below 380 nm), are invisible to us without special devices, although they can affect the senses in other ways.

Every vision process follows the same path when a photon of visible light is absorbed by the visual pigment of the photoreceptor in the retina (the light-sensitive part of the eye). This event initiates a series of chemical reactions, as a result of which a quantum of light is converted into an electrical signal, processed in the brain.

Two-photon vision is a phenomenon in which the human eye can perceive ultrashort pulses of infrared lasers with a wavelength in the range of 800-1300 nm by absorbing two photons. This process causes isomerization of visual pigments, which leads to the perception of light with a wavelength corresponding to half the infrared wavelength. Although these lasers are outside the visible range of the spectrum, their effect on visual pigments allows infrared light to be recorded as different colors.

Two-photon vision differs from single-photon vision primarily in the way light is absorbed. In single-photon vision, each photon with a specific energy is absorbed by molecules in the eye, which allows light to be perceived in the visible range. In two-photon vision, on the other hand, two photons with half the energy are simultaneously absorbed by visual pigments, which leads to the perception of light with half the wavelength, which theoretically should not be visible.

Furthermore, the brightness of the two-photon stimulus varies with the square of the power of optical radiation, so light scattered in the eye will not be perceived. Brightness also depends on the focus of the beam on the observer’s retina – the received stimuli are sharper and have better contrast than in the case of “normal,” single-photon vision.

ICTER scientists have long been studying the phenomenon of two-photon vision, were the first in the world to describe it, and now they have made another groundbreaking discovery.

On the picture: Oliwia Kaczkoś. Photo by Dr. Karol Karnowski.

A novel method for determining the brightness of two-photon stimuli

Two-photon vision shows potential in two key areas: medical diagnostics and virtual/augmented reality (VR/AR). It can be used for advanced diagnostic tests, especially in neurology and ophthalmology, where infrared pulses allow for safe monitoring of visual functions without the need to use visible light. On the other hand, this phenomenon allows the creation of new, realistic visual experiences by manipulating light stimuli from the infrared range, opening up new possibilities in interaction with virtual images (VR/AR).

All future applications of this phenomenon require knowledge of the luminance of two-photon stimuli, but the luminous efficiency function V(λ) outside the visible range is unknown. A non-standard approach to quantifying the luminance of two-photon stimuli is necessary, e.g., using infrared – which is what ICTER scientists did.

The method presented in the paper allowed the expression of the brightness of two-photon stimuli in photometric units. Thanks to the measurements performed, the scientists were able to demonstrate the relationship between the power of the infrared beam and the power of the visible beam, which was subjectively adjusted so that both were perceived as having the same luminance. Using the relationship between the power density of the VIS laser and the luminance of the projected stimuli, it was possible to determine the subjective luminance of the infrared stimuli using photometric units (cd/m2). These results emphasize the nonlinear nature of two-photon vision, which is in agreement with previous studies.

“The study aimed to develop a repeatable method for determining the brightness of stimuli for two-photon vision. Standard methods do not allow this to be done outside the visible spectrum of light, but our research opens the door to achieving this goal, which is necessary for further research and development of applications of this phenomenon in medical diagnostics and augmented reality (AR) and virtual reality (VR) technologies. The new approach will also enable comparison of the brightness of two-photon stimuli with traditional displays based on standard, single-photon vision”. – says Oliwia Kaczkoś, ICTER PhD student and optometrist, lead author of the study.

From left: Dr. Katarzyna Komar and Oliwia Kaczkoś. Photo by Dr. Karol Karnowski.

A platform for further discoveries

The result of the research is the proposal of a completely new physical quantity, called two-photon retinal illumination, which is sufficient to describe systems emitting two-photon stimuli. This relationship allowed the prediction of the luminance values ​​of two-photon stimuli, which could reach 670 cd/m2 in the safe laser power range of the human eye without adaptive optics (AO) correction.

Moreover, ICTER scientists documented twice the repeatability for measurements made on a background with a luminance of 10 cd/m2. This is crucial for the development of future technologies, such as two-photon retinal displays, which could be used in augmented reality (AR) glasses or in advanced diagnostic tools such as two-photon microperimetry.

Authors of the paper “Method for determination of luminance of two-photon vision stimuli”: Oliwia Kaczkoś, Agnieszka Zielińska, Jacek Pniewski, Maciej Wojtkowski, and Katarzyna Komar.

Author of the press release: Marcin Powęska.

Photos: Dr. Karol Karnowski.


ICTER, or the International Centre for Translational Eye Research, is a research, development and innovation centre at the Institute of Physical Chemistry of the Polish Academy of Sciences (IChF), located in Warsaw, Poland. ICTER was established in 2019 to develop cutting-edge technologies to support the diagnosis and therapy of eye diseases, based on funding from the International Research Agendas Programme of the Foundation for Polish Science, co-financed by the European Union – European Regional Development Fund. The centre is currently implementing the MAB FENG grant of the Foundation for Polish Science. In 2024, IChF has won a prestigious grant under the Teaming for Excellence / WIDERA program of Horizon Europe, which will enable ICTER unit to develop into a European centre of excellence. The centre’s website is: www.icter.pl.

02.10.2024

The technology that conquered rapid eye movements

A special camera, laser, and computer will provide an even more precise view of what is happening inside our eyes, according to researchers from the ICTER research centre. The new examination is painless and takes only 8.6 milliseconds, which is equivalent to the time it takes for a bee to flap its wings twice. This technology aims to enhance the detection of eye diseases at their early stages.

The technology, known as STOC-T, developed by scientists, has the potential to replace today’s OCT examination, commonly referred to as eye tomography. The team behind this new technology is led by Professor Maciej Wojtkowski, the head of ICTER. Notably, a quarter of a century ago, he created the first prototype of the OCT device, which is now used in ophthalmology clinics worldwide.

Capturing the eye in stillness

“In eye examinations, time is crucial. The eye constantly makes small, unconscious movements. Even though the previous technology only required a few seconds for an examination, each of these movements introduced noise, reducing the clarity of the results,” explains Professor Maciej Wojtkowski.

The development of digital technologies provided a solution. Researchers utilized a camera capable of capturing up to 60,000 frames per second, which is over a thousand times faster than standard smartphone cameras. As a result, the examination time was reduced to less than 0.01 seconds.

“During this imperceptible fraction of a second, our system illuminates the eye with multiple laser light waves. The camera captures hundreds of frames showing how the light propagates within the cells of the eye. These frames are then superimposed and analyzed by our software, which generates a precise image of the eye’s layers,” says Professor Maciej Wojtkowski.

This approach provides ophthalmologists with a detailed image of the retina, enabling them to detect early signs of various eye diseases, including glaucoma, macular degeneration, and diabetic retinopathy. The increased precision of diagnosis is particularly important in Poland, where one ophthalmologist serves approximately 10,000 patients. According to the latest report from the National Health Fund, more than half a million Poles are currently on waiting lists for ophthalmology appointments. Early diagnosis allows for quicker treatment, which, in many cases, can prevent vision loss.

International support

The ICTER research centre is part of the Institute of Physical Chemistry of the Polish Academy of Sciences. Its scientists combine knowledge from physics, biology, chemistry, engineering, and medicine. This interdisciplinary approach allows them to create new methods for examining and treating vision.

The developed technology is one of many steps planned by researchers. Their primary goal is to find a technological solution that will facilitate faster access to specialized ophthalmic care. Their efforts have been made possible by a prestigious grant awarded under the “Teaming for Excellence” program in Horizon Europe. They have secured €30 million in funding, half of which comes from the European Commission, with the remaining amount provided by the Foundation for Polish Science and the Polish Ministry of Education and Science.

With this funding, ICTER will establish a Centre of Scientific Excellence in Warsaw — a place where science meets practice, and research is transformed into concrete medical solutions. Partners in this project include the Institute of Ophthalmology at University College London and the Institut de la Vision at Sorbonne Université.

25.06.2024

A new way to monitor eye microcirculation. Multiwavelength laser Doppler holography (MLDH) in time-frequency optical tomography OCT (STOC-T)

For the eyes to function properly, they must be adequately supplied with blood, and abnormalities in the microcirculation may indicate dysfunctions in other arteries, which are difficult to examine. For the first time, scientists from the International Centre from Translational Eye Research (ICTER), operating within the Institute of Physical Chemistry of the Polish Academy of Sciences, used multiwavelength laser Doppler holography to assess blood flow in various layers of the human retina in vivo, which may impact the diagnosis of circulatory disorders.

Spatio-temporal optical coherence tomography (STOC-T) is a novel method for fast and aberration-free three-dimensional retinal imaging in vivo. In previous research, ICTER scientists used a multimode optical fiber, i.e. one that at its end emits several hundred non-repeating spatial patterns in the cross-section of the beam (so-called transverse modes) to obtain hundreds of OCT images which, when added together, reduce undesirable effects, including: speckle noise.

It turns out that the data set obtained during the STOC-T study can be processed in such a way as to reveal blood flow in the human retina. Classically, visualization of blood vessels requires at least two volumes. Subtracting them from each other allows you to determine voxels whose intensity changed during the measurement. From there images of blood vessels are generated. However, this approach requires very fast repetition times, which are not available in STOC-T. To solve this problem, ICTER scientists have developed a new method, called multiwavelength laser Doppler holography (MLDH), which allows the generation flow images from one volume, which may revolutionize the way of monitoring not only the microcirculation of the eye but also the condition of the entire body.

The research was carried out by Dawid Borycki, Egidijus Auksorius, Piotr Węgrzyn, Kamil Liżewski, Sławomir Tomczewski, Karol Karnowski and Maciej Wojtkowski from ICTER, and the results were published in the journal Biocybernetics and Biomedical Engineering in a paper titled “Multiwavelength laser Doppler holography (MLDH) in spatiotemporal optical coherence tomography (STOC-T)“.

What is microcirculation?

Microcirculation is the part of the cardiovascular system located between the arterial and venous systems. Microcirculation consists of vessels with a diameter of less than 150 μm, called capillaries. Arterial and venous elements are connected by “bridges” called metarterioles, from which some of the capillaries branch off. They contain the so-called precapillary sphincters, which regulate blood flow through the capillaries. The task of microcirculation is to deliver nutrients, exchange gases and metabolites, as well as regulate thermal and humoral processes.

Due to their unique accessibility, retinal arteries enable easy assessment of early vascular changes in vivo. Changes in retinal microcirculation mean global changes in the circulatory system, and therefore potential cardiac disorders. Additionally, pathological changes detected during the assessment of retinal microcirculation are one of the first signs of organ damage, which may precede, for example, proteinuria.

The retina is vascularized by two vascular systems: the choroid, which primarily supplies cones and rods; and the central retinal artery, mainly feeding the nervous tissue in the inner layers. The two systems differ in the amount of blood flow, which is much higher in the choroid than in the retinal vessels. Moreover, in the choroid, there are also significantly lower differences in blood oxygenation between arterial and venous vessels. When assessing retinal microcirculation, it is very important to precisely determine the measurement site.

Since the invention of the first ophthalmoscope in 1851 by Helmholtz, the fundus of the eye has been assessed. Even though this test was not very accurate, it allowed a small extent to assess the damage to the retinal microcirculation in the course of various diseases. In 1939, a 4-stage classification of hypertensive angiopathy and the relationship between subsequent stages of retinal vessels and an increased risk of a cardiovascular event were presented.

The study of retinal vessels has undergone a huge revolution, especially noticeable in the last 30 years. Currently, there are many tools available to assess the diameter of the vessel, the thickness of its wall, or the speed of blood flow based on the assessment of flowing erythrocytes or leukocytes. Another one just appeared.

Laser Doppler flowmetry and its modifications

One of the first non-invasive methods for assessing retinal microcirculation was laser Doppler flowmetry (LDF). In the early 1980s, it began to be more widely used in the study of flows in tissues and organs. This method uses a helium-neon laser with a wavelength of 632,8 nm.

Light is reflected from red blood cells moving in the vessels and from the solid, motionless surface of the skin. LDF results are presented as erythrocyte flow values ​​expressed in arbitrary perfusion units (PU), as it is not possible to calibrate the measurement to physiological units. This is not an ideal method because it assumes that the examined area should remain completely still, otherwise, artifacts will be created that affect the result.

An extension of LDF is scanning laser Doppler flowmetry (SLDF), which allows not only the assessment of retinal microcirculation parameters but also the morphology of the arterioles themselves. In turn, bidirectional laser Doppler flowmetry (BLDV) involves a complete assessment of the flow velocity of erythrocytes in the retina.

The Doppler spectrum of the laser can be decomposed to obtain the velocity distribution of moving cells. Recently, a similar approach was used to visualize in vivo velocity-resolved images of human retinal blood flow. For this purpose, laser Doppler holography (LDH) was introduced and used, in which the shifted Doppler optical field, backscattered from the retina, is detected using a holographic or interferometric full-field optical system.

A new technique for imaging eye microcirculation

Both LDF and LDH use light with a fixed wavelength. For this reason, both techniques in their original implementation do not provide detailed information about blood flow encoded in the optical field, which changes over time due to movement. A very interesting approach is the combination of dual-beam Doppler with optical tomography (OCT), which enables imaging and assessment of retinal layers. This, in turn, allows for simultaneous assessment of blood velocity and blood flow in the retinal vessels.

ICTER scientists recently demonstrated that by spatially modulating the phase of incident light, the laser’s spatial coherence can be reduced. Using a technique called spatio-temporal optical coherence tomography (STOC-T), it is possible to obtain many different OCT images, which, when averaged, allow for the removal of noise and distortions. This approach allows for in vivo imaging of the choroid with high spatial resolution.

It turns out that the same dataset can also be used to extract dynamic images of blood flow in the human retina. Individual two-dimensional STOC-T images, after appropriate digital correction, can be used to increase time resolution and obtain flow images. Now, a team led by Dr. Dawid Borycki has developed and tested an innovative method using STOC-T tomography to improve the visualization of blood flow in the human retina in vivo using the so-called multiwavelength laser Doppler holography (MLDH). It combines laser flowmetry with holographic multiwavelength detection, allowing non-invasive visualization and quantification of blood flow in various layers of the retina. This is possible at high blood cell flow rates and with high resolution. This combined approach enables effective assessment of eye microcirculation and, ultimately, extrapolation of the obtained results to the entire circulatory system.

  • Our method enables the acquisition of two-dimensional images of blood flow en face from a stack of interferometric images with different wavelengths recorded in ~8.5 ms. This time is comparable to the time needed in the case of conventional optical OCT (assuming a scanning frequency of 100 kHz) to register a pair of repeated cross-sectional scans, from which a one-dimensional image of blood flow can be obtained – says Dr. Dawid Borycki from ICTER, one of the authors of the newly published work.

It is worth adding that the implementation of MLDH does not require any modification of the standard STOC-T tomography protocol because this method uses blood flow information from the same data set. Therefore, MLDH can be considered a valuable extension of STOC-T tomography, which gives a complete picture of what is happening in our retina.

Author: Scientific Editor Marcin Powęska.

Publication:

“Multiwavelength laser doppler holography (MLDH) in spatiotemporal optical coherence tomography (STOC-T)” authors: Dr. Dawid Borycki, Dr. Egidijus Auksorius, Piotr Węgrzyn, Dr. Eng. Kamil Liżewski, Dr. Eng. Sławomir Tomczewski, Dr. Karol Karnowski, Prof. Maciej Wojtkowski.

Photo description: Nature repeats patterns in the most unexpected yet ordinary places. Just like the intricate network of blood vessels in the human eye, the tree branches in a park create mesmerizing patterns. In this photo, Dawid, the first author of our latest paper on retinal blood vessel imaging, admires the natural beauty of the trees nearby.

Photos: Dr. Karol Karnowski.

24.06.2024

ICTER is changing into a Centre of Excellence! “Teaming for Excellence” competition within Horizon Europe resolved

The International Centre for Eye Research (ICTER) is one of the winners of the prestigious “Teaming for Excellence” competition within Horizon Europe (HE). The funding will allow the establishment of a Centre of Excellence. ICTER’s current mission – creating modern ophthalmic diagnostic tools and combating eye diseases affecting over 250 million people worldwide – will be implemented on an even larger scale.

The Institute of Physical Chemistry of the Polish Academy of Sciences (IChF), under the Translational Research and Innovation in Ophthalmology Vision – Centre of Excellence (TRIO-VI CoE), will elevate the existing sub-unit, the International Centre for Translational Eye Research (ICTER), to a Centre of Scientific Excellence. The new Centre for Scientific Excellence will operate in Warsaw and will be established in cooperation with strategic partners: the Institute of Ophthalmology from University College London and the Institut de la Vision at Sorbonne Université. ICTER CoE will continue the Centre’s mission to date, which is to advance new technologies leading to the development of new eye treatment methods in the fields of minimally invasive surgery, biochemical control of protein machinery, genetic repair of inherited diseases, and tissue engineering; and also, the advancement of optical imaging technology and state-of-the-art robotics to assist in eye surgery and drug delivery.

The project leader is Prof. Maciej Wojtkowski, who almost 25 years ago built the first laboratory system for examining the retina and changed the paradigm of eye imaging.

ICTER CoE is a milestone aimed at unleashing the full scientific and commercialization potential of ICTER and intensifying its impact on society, science, education, and health by accelerating the introduction of therapies and new solutions in eye protection. The project is a response to the growing global health problem associated with eye diseases – lack of early diagnosis for many diseases, lack of effective therapies slowing down the progression of the disease, and – most importantly – lack of effective methods of restoring vision. The ambitious goal of ICTER CoE is to contribute to overcoming each of the above barriers, improving patients’ quality of life, and reducing the burden on national healthcare systems.

The main scientific goal of the ICTER CoE is to thoroughly investigate the dynamics and plasticity of the human eye, which will translate into the development of new therapies and diagnostic tools. The most important challenges facing the ICTER CoE include:

• creating modern methods of optical eye imaging and diagnostic tools for ophthalmological practice;

• deciphering the mechanisms of eye diseases – both rare and common;

• developing gene therapies and alternative methods of treating existing vision disorders;

• educating and training young scientists and doctors;

• creating a virtual eye clinic;

Centres of Excellence are a way to develop the best research institutes

Creating new or improving existing Centres of Excellence is an effective instrument for including Polish scientific and research institutions in the world elite. In our country, there are currently 4 projects implemented as part of the “Teaming for Excellence” programme, and three more are now joining. In addition to ICTER, the Astronomical Center named after Nicolaus Copernicus Polish Academy of Sciences (Astrocent Plus) and Łukasiewicz Research Network – PORT Polish Center for Technology Development (P4Health). Poland is the only country that received funding for three projects in this prestigious competition.

Each project will last six years and will receive a grant from the Horizon Europe Framework Program in the amount of 15 million euros. The funds from the European Commission will be supplemented by the Foundation for Polish Science under the MAB FENG program (8 million euros) and by the Ministry of Science and Higher Education (7 million euros).

We congratulate the other winners of the competition and look forward to the success of the Centres of Excellence being created.

Author: Scientific Editor Marcin Powęska.

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