Induced expression of progerin in retinal organoids

Abstract

The retina plays a very important role in our daily lives. It is the part at the inside, back of our eye that carries the photoreceptors. These cells receive the light and enable us to see the world around us. With the help of reprogrammed human stem cells, it is possible to create human retinas in vitro. The possibility of cultivating such retinal organoids as a 3D-cell culture presents us with the opportunity to further study the growth and development of this important part of our eye not just in its intact but also in a defective form. This study concerns itself with both the development of the retina in vitro and also with the effect of aging on retinal tissue. Through the induced overexpression of progerin, a protein that is typically expressed during the process of aging in tissue, it was possible to simulate this process and to discover its specific effects on the development and maturation of the retina. The retinal organoids were created through first culturing stem cells in a two dimensional cell culture environment and then gradually starting the process of differentiation towards the direction of the retinal tissue eventually resulting in 3Dcultures of the desired organ. Over the course of 200 days, those organoids were treated with progerin at different intervals in order to see a previously unknown effect and to gain a better insight into the impact that the overexpression of progerin actually has on the tissue and its properties. It was discovered that, in comparison to untreated controls the induced overexpression of progerin had an effect on both the physical appearance of the retinal organoids and also on the expression of retinal markers such as the proteins Recoverin, RBPMS, PKCa or CRX. These kinds of aging studies are still at an early stage, but they represent the opportunity to intensely study the effects of aging on human organs and, furthermore, to discover treatments to prevent blindness at later stages of life and as well as to study the development of retinal dystrophies over the course of a lifetime.

Date of Award	2025
Original language	English
Supervisor	Nicole Ollinger (Supervisor)