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Publication: Photoreceptor Survival Is Regulated by GSTO1-1 in the Degenerating Retina


Authors: Fernando N*, Wooff Y*, Aggio-Bruce, Chu-Tan J, Jiao H, Dietrich C, Rutar M, Rooke M, Menon D, Eells JT, Valter K, Board PG, Provis J, Natoli R.

* = Shared first authorship

Congratulations to Yvette Wooff (pictured) and Nilisha Fernando from Clear Vision Research whose work was recently accepted for publication in IOVS. Also, congratulations to Yvette Wooff who also won best the Radiation Oncology Private Practice Trust Fund Award for the Best Laboratory Research Poster at the Canberra Health Annual Research Meeting 2018 (CHARM).

This work was funded by grants secured by Dr Nilisha Fernando from Clear Vision Research from the Gretel and Gordon Bootes Medical Research and Education Foundation, and Professor Philip Board from the National Health and Medical Research Council of Australia (NHMRC, Project Grant APP1124673).

For more details on the work please see below:

Glutathione-S-transferase omega 1-1 (GSTO1-1) is a member of a family of glutathione S-transferase enzymes, with many reported roles including in modulating oxidative stress and inflammation pathways in various organ systems, where both overexpression and polymorphisms in the encoding gene have been linked to pathological diseases including cancer, and neurological disorders. However, the role of GSTO1-1 in modulating oxidative stress and inflammation in the normal and degenerating retina is currently unknown. The aim of this study was therefore to investigate the role of GSTO1-1 in modulating oxidative stress and consequent inflammation in the retina.

Results from this study firstly demonstrated that GSTO1-1 was localized to the inner segment of cone photoreceptors in the retina. Photoreceptors have one of the highest oxygen consumption levels of any cell type in the body, and are considered the major site of reactive oxygen species (ROS) production in the retina and are highly prone to oxidative damage. Therefore the suggested cellular location of GSTO1-1 combined with the known role of GSTO1-1 as a modulator of oxidative stress, indicates a potential role of GSTO1-1 in modulating oxidative stress in the retina.

In addition, using mice deficient in GSTO1-1, we demonstrated that following 5 days in 100,000 lux light (photo-oxidative damage (PD), Gsto1-/- mice had decreased photoreceptor cell death as well as decreased expression of inflammatory and oxidative stress markers. Further, retinal function in the Gsto1-/- PD mice was increased compared to WT PD mice. These results indicate that GSTO1-1 has a damaging effect in retinal degenerations as it is required for inflammatory-mediated photoreceptor death.

Knocking out GSTO1-1 reduced oxidative stress and inflammation, and related photoreceptor cell death in the retina in a model of retinal degenerations. Therefore targeting GSTO1-1 may be a useful strategy to reduce oxidative stress and inflammation and ameliorate photoreceptor loss, slowing the progression of retinal degenerations.

The full publication can be read at:

https://iovs.arvojournals.org/article.aspx?articleid=27

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