# The differential behavior of Prph2/Rom1 in rods and cone contributes to Prph2-associated disease heterogeneity

> **NIH NIH F31** · UNIVERSITY OF HOUSTON · 2021 · $39,844

## Abstract

PROJECT SUMMARY
Mutations in Peripherin 2 (PRPH2) account for a significant portion of inherited retinal diseases (IRD).
Delineating the role of PRPH2 in photoreceptor morphogenesis and rim formation is vital to understand how
mutations in a single protein could contribute to such diverse group of pathologies, ranging from retinitis
pigmentosa (RP) to pattern dystrophy (PD) and macular degeneration (MD). Even patients with intrafamilial
mutations can exhibit a notable degree of phenotypic variability, attesting to the complex nature in which PRPH2
functions. My objective in this application is to advance our current knowledge of the role of PRPH2 in outer
segment (OS) formation in order to have a better understanding of disease pathogeneses and for future
development of effective therapeutic strategies. Over the years, our lab has developed an extensive toolbox of
in vitro and in vivo mutant models, and are currently exploring innovative imaging techniques to further our
understanding of the role of Prph2 in OS landscape. Thus far, it has been determined that the association
between Prph2 and its homologue, Rod OS Protein 1 (Rom1), contributes significantly to the phenotypic
variability observed in patients and that lowering Rom1 levels could shift a sever Prph2-assocaited PD phenotype
to milder RP. Furthermore, it is know that the proper function of Prph2 at the disc rim is contingent upon proper
complex assembly of Prph2-oligomers and Prph2/Rom1-complexes. The central focus of this investigation
is to understand how Prph2 and Rom1 function differently in rods and cones with particular interest in
Prph2 homo- and Prph2/Rom1 hetero-complex formation/trafficking, and the effects of Prph2 mutations
on these processes. We propose two aims to address these goals: Aim 1 will assess the role of Rom1 in
cones and the mechanism by which it modulates Prph2-disease phenotypes. By eliminating or overexpressing
Rom1 in Prph2-disease models, we will conduct careful biochemical, structural, and functional analyses to
assess phenotypic differences, as they pertain to complex assembly and OS trafficking. Aim 2 will investigate
the role of interacting partners in the differential behavior of Prph2 in rods vs cones. In order to properly traffic
and function in the OS, Prph2 forms membrane microdomains to organize and house a network of proteins that
are necessary/specific for the formation of the closed rims in rods and open lamellae/rims in cones. In this aim,
we will identify critical Prph2 binding partners and determine how these interactions differ between rods and
cones. The outcomes of these studies will elucidate the specific function of Prph2 and Rom1 in rods and cones,
determine how modulating Rom1 affects disease phenotypes, and will further our understanding of the role of
Prph2 in the closed rim structure in rods and the open rim structures in cones. Given the lack of effective
treatments for Prph2-associated diseases, these studies are essential and b...

## Key facts

- **NIH application ID:** 10316059
- **Project number:** 1F31EY033216-01
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Larissa Ikelle
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,844
- **Award type:** 1
- **Project period:** 2021-09-28 → 2026-09-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10316059

## Citation

> US National Institutes of Health, RePORTER application 10316059, The differential behavior of Prph2/Rom1 in rods and cone contributes to Prph2-associated disease heterogeneity (1F31EY033216-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10316059. Licensed CC0.

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