Title: Pressure-related effects on retinal neurons and glia

Main supervisor: Patrik Midlöv

Reviewers: Maria Nilsson, Hammurabi Bartuma 

Abstract

Background

In glaucoma, ganglion cells, including their axons, are believed to be the primary target of insult. However, the exact disease mechanisms are unknown, and recent glaucoma-related studies have shown that other retinal neuronal subtypes and glial cells might be affected early. 

Research questions

Study 1

Is tissue damage in the adult porcine in vitro retina related to the time between enucleation and explantation? 

Study 2

How do inner neurons in the adult porcine in vitro retina change morphologically when subjected to different pressure levels? 

Study 3

How do Müller cells in the adult porcine in vitro retina react to different pressure levels? 

Study 4

Changes in individual retinal layers in patients with high intraocular pressure.

Results 

Study 1

The time between enucleation and explantation of the retinal was important. Retinas explanted after 240 minutes displayed profound tissue damage compared with 90 minutes counterpart. 

Study 2

After 24 hours, rod bipolar cell intensity was distinctly lower in explants subjected to 60-mmHg compared with 0-mmHg retinas.

Study 3

After 24 hours, Müller cells reacted to an increased pressure of up to 60-mmHg. 

Expected start in 2024.

Significance

Study 1 has given important insights into how to optimize in vitro experiments. In addition, the knowledge of pressure-related changes in retinal cells intimately connected with ganglion cells has increased. From a translational perspective, investigating retinal changes in patients with elevated pressure will be especially interesting. 

Published studies

Svare F, Åkerström B, Ghosh F. It's About Time: Time-Dependent Tissue Damage in the Adult Porcine Retina After Enucleation. CTO. 2021;210(1):58-65. doi: 10.1159/000514795. 

Svare F, Ghosh F. Beneficial and Detrimental Pressure-Related Effects on Inner Neurons in the Adult Porcine In Vitro Retina. Transl Vis Sci Technol. 2023 Feb 1;12(2):19. doi: 10.1167/tvst.12.2.19. 

Svare F, Ghosh F. Pressure-related effects on Homeostatic Müller cell proteins in the adult porcine in vitro retina. Accepted in Current eye research 231118. doi: 10.1080/02713683.2023.2286932