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ARVO 2024: Researchers drive innovation in retinal research
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A quartet of studies presented at the Association for Research in Vision and Ophthalmology’s 2024 Annual Meeting addressed diverse retina-related challenges and unveiled findings with the potential to revolutionize vision science.
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The retina is a vital processor of information for vision, and any damage can result in impaired vision. As a result, retinal research must stay on the cutting edge.
During the Association for Research in Vision and Ophthalmology’s (ARVO) 2024 Annual Meeting, 4 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 remains a puzzling disease for researchers. Its symptoms typically manifest during childhood and entail reduced night vision or vision in low light and loss of central vision.
According to a news release, more than 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).1
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”.
In order to a news release, on order to test the theory, the researchers 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.
According to researchers, their findings 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,” Méndez said in the news release. “We have established a mouse model that expresses the most prevalent disease-causing variant (D311N) in IMPDH1 and mimics the patients’ clinical signs."
Méndez further explained the mice will now allow researchers 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.
Novel approach in evaluating retinal processing impairment
The retina becomes more prone to damage as individuals age, and screenings are needed to head of signs of vision loss and preserve vision.
According to researchers, 1 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 of researchers from Northeastern University and New England College of Optometry in Boston, Massachusetts, developed a new method to assess retinal processing impairment called Angular Indication Measurement (AIM) dark adaptation.
According to the news release, this mmethod 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.1
Skerswetat explained 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,” Skerswetat concluded in the news release.
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.
According to the news release, 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.1
As it varies between individuals, it also varies across ethnicities. According to the news release, a team of researchers from the Northeastern State University College of Optometry in Oklahoma, Western University of Health Sciences College of Optometry in California, and EyePromise LLC in Missouri. 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.1
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,” Davey concluded.
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.1
Unfortunately, according to the news release, 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.1
According to the news release, 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,” Strachan concluded. “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.”
