Protein Linked to Mitochondrial Dysfunction Speeds Up Age-related Eye Disorders in Mice

Mutations in a protein called Tmem135 leads to disrupted mitochondrial activity and accelerates the progression of visual deficiencies, according to a new study.

The paper, “Mouse Tmem135 Mutation Reveals A Mechanism Involving Mitochondrial Dynamics Leading To Age-Dependent Retinal Pathologies,” was published in the journal eLife.

“Age-related macular degeneration (AMD), which affects roughly 11 million people in the U.S. alone, usually leads to loss of central vision — what you see when you look straight ahead — in both eyes,” Akihiro Ikeda, PhD, senior author of the study, said in a news release. “The vision becomes more blurred as time goes on, making it more difficult to read and even recognize people.”

He said there is there is currently no cure for either wet or dry AMD, and no proven medical treatments for dry AMD, which affects about 90 percent of AMD patients.

“Our study presents Tmem135, or the consequences of its defect, as potential new therapy targets for AMD and similar retinal conditions that occur later on in life.”

Tmem135 had already been associated with storage of fat and long life in studies using the worm C. elegans, but the exact role of this protein remained elusive.

Researchers found that mice carrying mutated Tmem135 presented retinal anomalies similar to those observed in mice aging normally, but at an earlier and faster pace. Additional analyses revealed that Tmem135 works by regulating the size of the mitochondria (the cells’ powerhouse) and that mutations in this protein disrupted mitochondrial activity in the retina.

“The regulation of mitochondrial size by Tmem135 determines the sensitivity of cells to environmental stress and the pace of aging in the retina,” said Wei-Hua Lee, the first author of the study. “On the other hand, mutations lead to higher sensitivity to such stress, showing that the protein is critical for protecting against this and for controlling the progression of retinal aging.

According to Lee, these results show that a single mutation can both accelerate aging and lead to age-dependent disease in mice, supporting the view that these two processes may be closely associated.

“Tmem135 may be a key molecule that could tip the normal aging process toward age-dependent diseases and potentially be explored for future treatments,” he said.

Future studies are needed to reveal the exact influence of Tmem135 on the mitochondria, and how that relates to aging and the development of age-related diseases.