Revolutionizing retinal research
Seattle, Wash. — The retina serves as a vital processor, enabling the transmission of visual information from the eyes to the brain. Damage to the retina can disrupt this process, causing the eye to still receive light but hindering the brain's ability to form images accurately. Various conditions can harm the retina, affecting overall eye health. Therefore, research must remain current and innovative. At the Association for Research in Vision and Ophthalmology’s (ARVO) 2024 Annual Meeting, four studies addressed diverse retina-related challenges and unveiled findings with the potential to revolutionize vision science.
Exploring retinitis pigmentosa mutations: New understanding emerges
Retinitis pigmentosa (RP) is a rare, hereditary eye disease that causes vision impairment. Symptoms typically manifest during childhood and entail reduced night vision or vision in low light and loss of central vision. With over 100 different genes implicated in RP when mutated, it is challenging to find a cure. Scientists in Spain studied a specific type of RP, autosomal dominant RP type 10 (adRP10), that is caused by mutations in the paternal or maternal copy of gene inosine monophosphate dehydrogenase 1 (IMPDH1).
Lead researcher Ana Méndez, PhD, and her team hypothesized that retinal neurodegeneration occurs because the enzyme is always active due to the loss of guanosine diphosphate (GDP) and guanosine triphosphate (GTP) “allosteric inhibition”. To test this, they tracked changes over time of the structure of the retina and visual function in mice with the D226N mutation, a mutation of IMPDH1, and without the mutation using electroretinography (ERG). They also evaluated the IMPDH1 cellular structure and observed the GDP and GTP levels in retinal cell/tissue extracts.
Their results indicated that IMPDH1 mutations at the Bateman domain that reduce the GDP/GTP allosteric inhibition in vitro led to the irreversible formation of rod-like structures within photoreceptor cells in vivo. These IMPDH structures usually represent a high-activity protein state, as they typically form in cells under conditions of increased GTP demand such as proliferating cells in other systems. “Mutations in IMPDH1 account for 0.1 to 2% of all cases of retinitis pigmentosa depending on the patient cohort, for which there is no current treatment.” said Méndez, “We have established a mouse model that expresses the most prevalent disease-causing variant (D311N) in IMPDH1 and mimics the patients’ clinical signs. These mice will now allow us to understand the impact of the mutation on nucleotide metabolism in vivo and to launch preclinical assays based on pharmacological and genetic strategies transferable to patients.”
- Abstract title: Basis of physiopathology in a novel murine model of autosomal dominant Retinitis Pigmentosa type 10 by mutations in Inosine Monophosphate Dehydrogenase 1
- Presentation start/end time: Sunday, May 5, 3:15 – 5pm PT
- Location: Exhibit/Poster Hall, Seattle Convention Center - Arch Building
- Posterboard number: B0169
Novel approach in evaluating retinal processing impairment
The retina is vulnerable to permanent damage as people age. Hence, people need to receive regular screenings to detect signs of vision loss to preserve good vision. One biomarker for outer retinal processing impairment is delayed dark adaptation, a condition where the eyes, specifically the retinas, take longer than usual to adjust to low light situations after being exposed to bright light. Lead investigator, Jan Skerswetat, PhD, and a team from Northeastern University and New England College of Optometry in Boston, Mass. developed a new method to assess retinal processing impairment called Angular Indication Measurement (AIM) dark adaptation.
This method was designed to evaluate the time course of retina’s adjustment to low light after continuous bright flashes by measuring contrast sensitivity for oriented C optotypes. The scientists tested the AIM dark adaptation paradigm on patients with macular disorders and healthy control participants. They found that it was able to rapidly and accurately measure how quickly contrast sensitivity recovered after exposure to bright light in both groups and they detected a notable delay in dark adaptation recovery among patients with macular disorders. Skerswetat expressed, “The AIM Dark Adaptation method provides a swift and individualized evaluation of the retina's capacity to recover from photostress, a functional biomarker of age-related and inherited retinal impairments. With its ability to rapidly assess dark adaptation without the need of a pre-test adaption phase and special equipment, AIM Dark Adaptation holds promise as a self-administered screening tool for early detection of age-related macular degeneration, a condition impacting an estimated 196 million individuals globally.”
- Abstract title: Angular Indication Measurement (AIM) paradigm applied to Dark Adaptation in patients with retinal disorders: preliminary results
- Presentation start/end time: Monday, May 6, 9:15 – 9:30am PT
- Location: Room 612 (Level 6), Seattle Convention Center – Arch Building
- Presentation number: 1486
Breaking new ground: Macular pigment optical density in Native Americans
Macular pigment optical density (MPOD) refers to a measure of pigments in the macula. The pigments are located near the center of the back of the eye and protect the retina from damage. Pigments can differ between individuals and fluctuate over time. It is important to measure MPOD because low macular pigment is a top risk factor for age-related macular degeneration (AMD). It’s also a risk factor and biomarker for diseases such as diabetes and diabetic eye disease.
As it varies between individuals, it also varies across ethnicities. Thus, scientists from the Northeastern State University College of Optometry in Okla., Western University of Health Sciences College of Optometry in Cali., and EyePromise LLC in Mo. studied MPOD between Cherokee Native Americans and Caucasians. All participants received a comprehensive eye exam that included MPOD evaluation, visual acuity, refraction, and anterior and posterior segment assessment.
Pinakin G. Davey, OD, PhD, lead investigator, said MPOD “is a direct and modifiable biomarker in health and disease state. The Native American MPOD levels are lower than Caucasian which may explain in part the greater prevalence and risk of retinal disease. Health initiatives through dietary and intake of nutritional supplement could provide the necessary protection and benefits.”
- Abstract title: A cross-sectional comparison of macular pigment optical density in a group of Native American and Caucasians
- Presentation start/end time: Wednesday, May 8, 2:15 – 4pm PT
- Location: Exhibit/Poster Hall, Seattle Convention Center - Arch Building
- Posterboard number: B0398
Insights into optic atrophy pathogenesis
Optic atrophy (OA) is an inherited condition that leads to the retinal ganglion cells, which form the optic nerve connecting the eyes to the brain, slowly and irreversibly degenerate. This will cause individuals with OA to progressively lose their vision, typically beginning in early life. Unfortunately, there is currently no cure or treatment to address the underlying causes, therefore slowing or preventing disease progression. Thus, more studies are needed to understand OA.
Elin Strachan, MSci, leader researcher, along with scientists from Ireland and France, focused on studying underlying disease-related alterations. It is known that many patients have mitochondrial fusion protein (OPA1) mutations but is uncertain why this mutation leads to the death of retinal ganglion cells (RGCs). Hence, they used zebrafish and fruit fly models to replicate the genetic changes related to OA.
They were successful in creating OA-related changes in the animal models seeing dysfunction in their cells and the progression of vision loss. Strachan said, “There are very limited treatment options for people with optic atrophy — my research aims to further our understanding of the underlying pathological changes in novel fish and fly models of optic atrophy. By better understanding how mitochondria are affected in the optic nerve specifically, we are better placed to treat and prevent sight loss caused by optic atrophy in the future.”
- Abstract title: Novel in vivo models of optic atrophy show pathological changes in mitochondrial structure and function
- Presentation start/end time: Monday, May 6, 3 – 4:45pm PT
- Location: Exhibit Hall - Seattle Convention Center
- Posterboard number: B0028
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The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include approximately 10,000 eye and vision researchers from over 75 countries. ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders. Learn more at ARVO.org.
Media contact:
Jenniffer Scherhaufer, MMC, CAE
1.240.221.2923
media@arvo.org