# Mechanisms that govern dopaminergic amacrine cell diversity

> **NIH NIH F32** · BAYLOR COLLEGE OF MEDICINE · 2022 · $67,174

## Abstract

Project Summary: Dopamine signaling in the retina is crucial for regulating circadian rhythms and circuit
reconfiguration for daytime vision. Reduced dopamine signaling is associated with many visual disorders and
pharmacological therapies using dopamine analogues have shown promise for treating diseases like diabetic
retinopathy. The primary source of retinal dopamine is the dopaminergic amacrine cells (DACs). This project is
focused on elucidating molecular mechanisms that govern the specification of these specialized amacrines.
This knowledge will enable the development of novel therapeutics that harness the power of regenerative
medicine to regrow repair or replace the dopaminergic amacrine cells and restore dopamine abundance to
normal levels. Toward this goal, we conducted a screen to identify molecules that, when deleted, increase
dopaminergic amacrine cell formation. We uncovered a candidate signaling pathway controlled by the serine-
threonine kinase LKB1. When LKB1 is deleted embryonically there is an approximate doubling of the
dopaminergic amacrines that persists into adulthood. Concomitantly there is an increase in dopamine when
measured by High Performance Liquid Chromatography. We hypothesize that LKB1 signaling is activating
developmental programs that restrict the abundance of the DAC population. Here we set out to
determine whether LKB1 signaling is required intrinsically in amacrine cell precursors as well as the temporal
requirement for LKB1 signaling to restrict DAC formation. We will also leverage the ability of super resolution
STORM microscopy to visualize the distribution and release of dopamine in the newly generated DACs. Our
second aim is to identify the downstream effectors from LKB1 that are required to restrict DAC formation. We
will utilize loss of function and rescue experiments of known molecules downstream from LKB1 such as AMPK
to test their contribution to DAC formation. We will also conduct single cell RNA sequencing to compare the
transcriptional landscapes between DACs in control vs mutant retinas. This will allow us to find additional
downstream candidates from LKB1 required for restriction of the abundance of DACs. This analysis is
compelling from the basic science perspective but will also define novel molecular targets for mitigating
dopamine neuron loss and restoring visual capacity. This knowledge may be useful for preventing
dopaminergic neuron defects beyond the eye, such as those that occur in Parkinson’s disease.

## Key facts

- **NIH application ID:** 10535384
- **Project number:** 1F32EY034358-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Robert Mackin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-09-30 → 2025-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535384

## Citation

> US National Institutes of Health, RePORTER application 10535384, Mechanisms that govern dopaminergic amacrine cell diversity (1F32EY034358-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10535384. Licensed CC0.

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