# Retinoid cycles and retinal disease treatment > **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2024 · — ## Abstract Project Summary Age-related macular degeneration (AMD) is a major cause of legal blindness in individuals over 60 years old including Veterans. It is characterized by central field vision loss where sharp, polychromatic images are formed under the well-lit conditions in which modern humans are immersed, which leads to significant disability. The high prevalence of AMD places a heavy burden on the healthcare system with upwards of 98 billion dollars spent yearly on AMD-related healthcare costs in the US. Currently, there are no highly effective treatments for the most common form of the disease, known as geographic atrophy, which makes up ~90% of advanced AMD. During the past VA funding period, we studied visual cycle modulation and phosphodiesterase inhibition as potential treatments for AMD and developed a novel mouse model to study a critical tissue involved in AMD pathogenesis. Based on key findings we made during this funding period, we now propose to investigate details of retinoid physiology and develop new retinoid-based treatments for retinal diseases including AMD. We can now quantitatively interrogate and define the cell-specific functions of retinoid-binding proteins and enzymes with multiple sites of expression within the body and leverage this information to more fully understand how to provide therapeutic benefits to Veterans suffering from retinal diseases. We will pursue these objectives through the following Aims: 1) Define cell-specific roles of cellular retinaldehyde-binding protein (CRALBP) in visual chromophore synthesis and photoreceptor function. CRALBP is a retinoid-binding protein that contributes to visual cycle function and is involved in a variety of retinal diseases. It is expressed in both the RPE and Müller glia cells of the retina. Data suggest these two pools of CRALBP play different roles in retinal physiology, but studies performed to date have produced conflicting results. Taking advantage of newly developed tissue-specific CRALBP knockout mice, we will investigate the role of this protein in photoreceptor function and retinal structure using a host of sophisticated electrophysiological, biochemical, and retinal imaging techniques. Our data are expected to provide critical information about tissue targeting for gene therapy approaches. 2) Evaluate the roles of lecithin:retinol acyltransferase (LRAT) in ocular retinoid homeostasis. LRAT is an enzyme critically involved in an ocular retinoid trafficking axis existing between the gut, the liver, and the RPE. This protein plays a key role in retinoid storage in the liver and is also crucial for visual function. Several outstanding questions remain regarding cell-specific functions of LRAT in determining retinoid distribution and maintenance within the eye. We will clarify the roles of LRAT in the RPE and the liver through tissue-specific LRAT knockout studies. We hypothesize that LRAT is crucial for both packaging of retinoids in the liver for delivery to the eye a... ## Key facts - **NIH application ID:** 10805758 - **Project number:** 2I01BX004939-05 - **Recipient organization:** VETERANS HEALTH ADMINISTRATION - **Principal Investigator:** Philip David Kiser - **Activity code:** I01 (R01, R21, SBIR, etc.) - **Funding institute:** VA - **Fiscal year:** 2024 - **Award amount:** — - **Award type:** 2 - **Project period:** 2020-04-01 → 2028-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10805758 ## Citation > US National Institutes of Health, RePORTER application 10805758, Retinoid cycles and retinal disease treatment (2I01BX004939-05). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10805758. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*