Posted on 20 Mar 2017

The Newly Discovered Role Played by GARP2 in Accelerating Retinal Degradation

Accelerating Retinal Degradation from GeneTargeting.comDiseases such as retinis pigmentosa have long been known to cause blindness and impaired visual function. Scientists at the UAB School of Potometry, led by Marci DeRamus, PhD and Steven Pittler, PhD, have extensively studied the role that rod cell proteins, GARP 1 and 2, have on normal phototransducion. Their study, published in Scientific Reports, seems to indicate that GARP 2 in particular can lead to an acceleration of retinal degradation in experimental mouse models. Moreover, the genetic background used in the study made it possible to amplify the effects of these proteins and shed new light on the role they play in normal vision.

The New OCT Nomenclature for Mice

Light-sensing rod cells form the first step toward translating light into electrical impulses and ensuring correct vision. DeRamus and Pittler have not only managed to measure retinal degradation in mice, but also came up with a special nomenclature for distinguishing the differences between mice and humans in this regard.

Non-invasive imaging tests were used to create a clear picture of the retina’s various layers, and measure its integrity. Through the use of optical coherence tomography (OCT), the researchers proposed a new type of labeling for mice that would no longer be in conflict with current OCT nomenclature, as accepted for humans.

In order to achieve this, the researchers at UAB aligned mouse OCT imaging with histologic imaging. This alignment offered accurate layer designation for all mouse models, and promoted a single standard for layer designation that the scientists also used in their own research.

According to one of the professors at the UAB Department of Ophthalmology, Christine Curico, PhD, this change will facilitate as stable standard for mice that is just as effective as the OCT standard doctors use to diagnose retinal disease, and could lead to more efficient laboratory studies in the future.

What Did the Study Consist of?

The main problem with GARP 1 and GARP 2 was that their roles are confused since they stem from the same gene and consist of more than 300 identical amino acids. GARP 1 features 232 more amino acids, and their disorganized nature cause difficulty in establishing their interaction with other proteins.

A knockout mouse model was developed that lacked a rod protein known as cGMP-gated cation channel beta-subunit. It also lacked the GARP proteins, both encoded by that gene.

The mice were then bred with three other types of knockout mice that had either only GARP1, only GARP2 or both proteins. Following this course of action, retinal degradation was observed over a course of three and ten weeks. With the use of light and transmission microscopy and OCT, the outer nuclear layer was measured, and functional loss was accurately described through the process of electroretinography.

Results of the Study

The beta-subunit knockout mice that only had GARP2 experienced the highest rate of thinning of their outer nuclear layer. The same group also experienced the greatest rate of full retinal thinning when compared to normal mice. In each cases, the group was followed by the knockouts that had both GARP 1 and 2, and by the GARP1-only mice.

These results seemed to suggest GARP2 played the most important role in accelerating retinal degradation. Also, it’s worth mentioning that GARP1 actually had the effect of slowing down the damage caused by GARP2, showing that the proteins have very different roles despite their overall similarity.