CIB2 Regulates mTORC1 in Photoreceptor Autophagy

Article: Recycling of the Eye’s Light Sensors Is Faulty in Progressive Blindness of Older Adults
Source: University of Maryland School of Medicine, via ScienceDaily
Published: June 23, 2021
Article: Macular Degeneration Linked to Inability to Remove Damaged Photoreceptors
Source: Genetic Engineering & Biotechnology News
Published: June 24, 2021

Photoreceptors (purple) accumulate in mouse eyes with CIB2
mutation (upper right). Undigested photoreceptor material
(yellow) in mouse eyes with CIB2 mutation (lower right).

Researchers studying the pathology of age-related macular degeneration (AMD) are looking into two proteins that play a role in photoreceptor autophagy, a process that is essential for proper light detection. Without this clean up by support cells, the undigested photoreceptor material accumulates over time, contributing to a toxic environment that eventually leads to retinal degeneration and potential vision loss. One protein called calcium and integrin binding protein 2 (CIB2) seems to be responsible for this photoreceptor maintenance; eyes of mice engineered without the CIB2 gene exhibited sub-retinal pigment epithelium (RPE) deposits, marked accumulation of drusen markers, reduced lysosomal capacity and autophagic clearance, and impaired visual function. The researchers also investigated the role of a protein called mTORC1. Involved in other human diseases such as cancer, obesity, and epilepsy, mTORC1 plays a regulatory role in processes such as cleaning up cellular debris. They found that mTORC1 was overactive in mice with CIB2 mutation and also overactive in human eye tissue samples from people with dry AMD. The mTOR protein comes in two varieties: mTORC1 and mTORC2. Because mTOR is involved in many other cellular processes, tinkering with it leads to major side effects. The researchers think regulating mTORC1 via CIB2 can bypass many of these adverse effects. One of the authors says, “Using the evolving understanding of the mechanistic role of mTORC1, this study has provided great insights into new ways that researchers can begin to find ways to preserve, to treat, and/or improve macular degeneration, and thus improve the quality of life and independent living in many older adults.”

My rating of this study: ⭐⭐⭐

Sethna S, Scott PA, Giese APJ, et al. "CIB2 regulates mTORC1 signaling and is essential for autophagy and visual function." Nature Communications.  12(3906). 23 June 2021.
https://doi.org/10.1038/s41467-021-24056-1