Sunday, July 6, 2025 7/6/2025

Genetic Modifiers of Enhanced S-cone Syndrome –Role of the External Limiting Membrane

Award Number: R01EY028561
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2024

Group Awards By:

View Award Description

Genetic Modifiers of Enhanced S-cone Syndrome –Role of the External Limiting Membrane - PROJECT SUMMARY/ABSTRACT Enhanced S-cone syndrome (ESCS) is an inherited retinal degeneration characterized by an increased number of S-cones, retinal dysplasia, and progressive photoreceptor degeneration leading to early night blindness and loss of visual acuity. The disease is caused by mutations in the rod-fate determining transcription factor NR2E3 in humans and the rd7 mouse model. The disease presentation is highly variable in human and dependent on genetic background in the mouse, demonstrating the existence of genetic modifiers. The mouse model demonstrates that the retinal dysplasia is intimately associated with the occurrence of breaks in the external limiting membrane (ELM), a network of adherens/tight junctions between Müller cell apical processes and photoreceptor inner segments. Fragmentation of the ELM is also observed in other retinal diseases associated with dysplasia, such as Leber's Congenital Amaurosis (LCA) due to mutations in crumbs1 (CRB1) and RP27, and in diabetic retinopathy. We have identified a genetic modifier that prevents the fragmentation of the ELM in both the rd7 mouse and the Nrl ko mouse (RP27) models. This discovery strongly suggests a causative role for the ELM fragmentation in the development of photoreceptor dysplasia and provides a tool with which to establish the mechanisms by which ELM breaks occur, how they lead to retinal dysplasia, and how this affects disease progression. In order to identify these mechanisms we will: 1) Determine the natural history of ELM junction formation and photoreceptor differentiation in wt and the rd7 model using marker analysis of cell junction proteins. 2) Identify the cell types involved in the ELM fragmentation by single cell RNAseq analysis. 3) Determine how the modifier protein alters recruitment of junctional proteins to the cell membrane. 4) Identify the molecular basis of additional genetic modifier strains that we have generated to gain further insight into the NR2E3 disease pathways.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	5	8/19/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $424,375 )
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	5	1/24/2022	NON-COMPETING CONTINUATION	$424,375
														Subtotal = $424,375

Issue Date FY: 2021 ( Subtotal = $424,375 )
2021	2021	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	4	1/26/2021	NON-COMPETING CONTINUATION	$393,750
2021	2021	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	001	4	4/21/2021	NON-COMPETING CONTINUATION	$30,625
														Subtotal = $424,375

Issue Date FY: 2020 ( Subtotal = $437,500 )
2020	2020	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	3	1/29/2020	NON-COMPETING CONTINUATION	$437,500
														Subtotal = $437,500

Issue Date FY: 2019 ( Subtotal = $437,500 )
2019	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	2	1/10/2019	NON-COMPETING CONTINUATION	$437,500
														Subtotal = $437,500

Issue Date FY: 2018 ( Subtotal = $437,500 )
2018	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	1	1/19/2018	NEW	$437,500
														Subtotal = $437,500

Grand Total All Awards = $2,161,250

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Genetic Modifiers of Enhanced S-cone Syndrome –Role of the External Limiting Membrane

Award Number: R01EY028561

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer