Author ORCID Identifier

https://orcid.org/0000-0002-4295-5441

Semester

Spring

Date of Graduation

2026

Document Type

Dissertation (Campus Access)

Degree Type

PhD

College

School of Medicine

Department

Biochemistry

Committee Chair

Visvanathan Ramamurthy

Committee Member

David Smith

Committee Member

John Hollander

Committee Member

Maxim Sokolov

Committee Member

Saravanan Kolandaivelu

Abstract

Protein chaperones, such as HSP90, are critical for maintaining proteostasis by maintaining proteins in functional states. We are interested in the cytosolic isoforms HSP90α and HSP90β because patients in clinical trials administered HSP90 inhibitors reported visual disturbances, specifically night blindness. Highlighting the sensitivity of photoreceptor function to impairment of HSP90 chaperones. Τhe highly homologous nature of cytosolic HSP90α and β paralogs and their ability to facilitate the maturation of the same clients imply that the HSP90 isoforms could compensate for one another. To address the question, a retina-specific conditional knockout of HSP90β (Hsp90ab1) was generated, revealing that loss of HSP90β alone does not disrupt retinal development, photoreceptor morphology, or visual function. To examine potential redundancy during photoreceptor development, mice lacking both cytosolic HSP90 isoforms in photoreceptors were generated. Although retinal lamination was preserved, photoreceptors failed to elaborate outer segments, and visual response was ablated. Our findings show that HSP90α is not essential for photoreceptor development but is vital for maintaining mature rod photoreceptor function and survival, and can fully compensate in the absence of HSP90β. Whereas HSP90β is able to compensate for the absence of HSP90α during the development of rods and long-term maintenance of cones. Altogether, our findings show unique and overlapping roles of cytosolic HSP90α & β in photoreceptors.

Download

Share

COinS