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Stopping Degeneration in its Tracks Part One

Posted by Ilena Di Toro | Posted on August 3, 2021

Retinitis pigmentosa is a group of rare genetic disorders that leads to the loss of retina cells. Symptoms include difficulty seeing at night or in low light conditions and the loss of peripheral vision. Age-related macular degeneration is a disease that blurs the central vision that you need for reading and driving. Both disorders are genetic and lead to a degeneration of vision. While there are treatments and aids to help those with these conditions, there are no cures.

Of course, researchers are studying how these disorders come about and what is going on in the genetic level so that better treatments can be developed and possibly even reverse these disorders.

Starting with retinitis pigmentosa, researchers at the University of Alabama Birmingham are studying certain rod proteins in the retina to learn how they function during the normal processing of light into electrical signals, known as phototransuction and how they function during the degeneration of the retina.

The proteins in question are GARP1 and GARP2 and scientists wanted to see the structure of these proteins and how they function in the light-sensing rods in the retina. Lead by Steven Pittler, PhD, researchers did experiments that showed GARP2 accelerated retinal degeneration in mice that didn’t have a rod cell protein that helped to produce the electrical signal. Not having this protein, both amplified the harmful effects of GARP1 and GARP2 and allowed their roles to be differentiated.

Yet, telling which protein does what, is obscured by the fact that they are generated by the same gene and are identical for 318 out of 326 of the amino acids that make up GARP2. Also, GARP1 has 550 amino acids and it has 232 that aren’t found in GARP2. On top of all that, GARP1 and GARP2 are disorganized proteins which allows for multiple formations that propel interactions with many proteins.

To learn which protein does what, scientists bred mice that didn’t have both a rod protein called cGMP-gated cation channel beta-subunit and the GARP proteins. Then they bred mice with just the GARP1, just the GARP 2 and both GARP1 and GARP2. They looked at retinal degeneration in these mice at three and 10 weeks using optical coherence tomography to measure the thinning of the layer that contains the rods and cones. Researchers also measured the thinning of the retina and functional vision loss.

Pittler’s lab found that the rate of thinning of the rod and cones layer, as compared to normal mice, was greatest in the group that just had GARP2, followed in descending order by mice with both GARP1 and GARP2 and mice with just GARP1 and mice without the GARP proteins. The rate of retinal thinning, as compared to normal mice, was greatest in the mice that just had GARP2, followed by mice with both GARP1 and GARP2, mice without the GARP proteins and mice with just GARP1.

It seems the GARP2 protein sped up retinal degeneration. Still, when both GARP2 and GARP1 were present, GARP1 slowed the negative effects of GARP2. This implies that GARP1 and GARP2 have distinct and separate roles in the rod photoreceptors.

It isn’t just the proteins that can lead to visual degeneration. Other compounds will be covered in the next blog entry.

Sources:
https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/retinitis-pigmentosa

https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration

https://www.uab.edu/news/research/item/8000-garp2-accelerates-retinal-degeneration-in-a-mouse-model

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