# Pigment Regeneration Mechanisms in the Human Retina

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $384,315

## Abstract

ABSTRACT
During the past 2-3 decades important work has been done to resolve the mechanisms of light and dark
adaptation as well as disease in the mammalian rod and cone photoreceptors using mouse as a model system.
However, the mouse is a nocturnal animal that lacks the macula, a specialized central region in primate retina
that provides high-acuity color vision critical for human everyday survival. Consequently, mechanisms of human
daytime vision or diseases that disrupt photoreceptors in the macula, such as Age-Related Macular
Degeneration (AMD), are challenging to study in mice. For example, there is no effective treatment for the dry
form of AMD, the most common cause of blindness among the elderly. Thus, there is a critical need to better
understand the biology of the photoreceptors in the human macula in health and disease. This is particularly true
of cone photoreceptors compared to rods that have been more extensively studied. Recent studies have
established both light-independent and light-dependent pigment regeneration pathways within the mouse retina
isolated from the pigment epithelium (RPE). These pathways regenerate pigment via Müller cells in cone-specific
pathways (light-independent and -dependent intraretinal visual cycles) or in the photoreceptor cells themselves
by a cell-autonomous regeneration mechanism. However, nothing is known about these mechanisms in the
human macula or fovea. The goal of this proposal is to determine the contribution of the RPE-independent
pigment regeneration pathways to the ability of cones to dark adapt quickly and maintain sensitivity in bright light
specifically in the human macula. Our central hypothesis is that the canonical visual cycle that operates via the
RPE is too slow to maintain vision in bright light or mediate dark adaptation during rapidly changing levels of
illumination in the human macula. The work is organized into two specific aims. These are to determine the
contribution of the light-independent intraretinal visual cycle (Aim I) and photic pigment regeneration pathways
(Aim II) to dark adaptation and maintenance of light sensitivity of human macular cones. The experiments will
employ ex vivo electroretinography and single cell suction electrode recordings. These techniques are well
suited for assessing the role of visual cycles and cell-autonomous pigment regeneration pathways in dark
adaptation and maintenance of light sensitivity, respectively. We will leverage our experience and collaborations
with Eye Banks that we have established during the past three years to develop donor criteria and protocols to
record light-evoked responses of macular cones from organ or research donor human eyes 1 – 5 hours
postmortem. Results of these studies will determine the contribution of different visual cycle pathways to human
vision mediated by the cones across geographical regions of the retina, including the fovea. This information will
provide a basis for studies to elucidate pathogenesis ...

## Key facts

- **NIH application ID:** 10450119
- **Project number:** 5R01EY031706-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Frans Vinberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,315
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450119

## Citation

> US National Institutes of Health, RePORTER application 10450119, Pigment Regeneration Mechanisms in the Human Retina (5R01EY031706-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10450119. Licensed CC0.

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