Department of Biology

University of Kentucky

Lexington, KY

BASIC RESEARCH PROJECT

Analyzing the functional role of calycleal processes in DCHR1-dependent cone rod dystrophy

Research Interests

This project seeks to enhance our understanding of the molecular mechanisms underlying cone-rod dystrophy (CRD), particularly in relation to the loss of CDHR1 function. CDHR1 is a specialized protein found in the retina and has been linked to CRD in many human patients. It is believed that CDHR1 plays a role in connecting newly forming rod outer segment discs to the inner segment, influencing their maturation and release. However, we still don’t fully understand how the loss of CDHR1 leads to CRD, especially in relation to cone photoreceptors and how they are affected

Plans for 2024

In our efforts to decipher CDHR1’s role in zebrafish cones, we made a novel discovery. We found that CDHR1 may form connections between photoreceptor outer segments and inner membrane extensions called calyceal processes by physically interacting with a specific cadherin called Pcdh15b. Based on this finding, we aim to test the hypothesis that these connections are essential for maintaining and assembling rod and cone outer segments, and that their disruption leads to CRD. To test our hypothesis, we’ve created a zebrafish mutant with a non-functional cdhr1a gene, which exhibits key features of CRD, including early and severe degeneration of cone photoreceptors and delayed degeneration of rods.

To test our hypothesis we propose the following aims:

1. Characterize the integrity of calyceal processes in the absence of Cdhr1a function.
2. Examine the functionality of Cdhr1a-Pcdh15b interactions.
3. Visualize interactions between Cdhr1a and Pchd15b in photoreceptors in vivo.
4. Identify the cdhr1a outer segment interactome.

Overall, our project aims to comprehensively study the interaction between outer segments (via cdhr1a) and calyceal processes (via pchd15b) to establish a novel mechanism critical for maintaining outer segment health and preventing CRD. Our research may also uncover additional genes involved in this mechanism, potentially identifying new target genes associated with CRD.