Abstract
Purpose :
Aging is one of the most significant pathogenic factor for several retinal degenerative diseases, such as age-related macular degeneration. Zinc metallopeptidase STE24 (ZMPSTE24) is a metalloprotease involved in processing lamin A, a major structural protein of nuclear envelop. In humans, Zmpest24 mutation led to severe premature aging diseases because of production of immature prelamin A and abnormal nuclear structure. The effects of ZMPSTE24 deficiency remain largely unknown in retina. Here, we use Zmpest24 knockout (KO) mice as a model to study premature aging in retina upon light damage (LD).
Methods :
Aging is one of the most significant pathogenic factor for several retinal degenerative diseases, such as age-related macular degeneration. Zinc metallopeptidase STE24 (ZMPSTE24) is a metalloprotease involved in processing lamin A, a major structural protein of nuclear envelop. In humans, Zmpest24 mutation led to severe premature aging diseases because of production of immature prelamin A and abnormal nuclear structure. The effects of ZMPSTE24 deficiency remain largely unknown in retina. Here, we use Zmpest24 knockout (KO) mice as a model to study premature aging in retina upon light damage (LD).
Results :
No significant retinal morphology or functional impairment was detected in Zmpest24 KO and WT mice without LD. However, LD led to increased photoreceptor death, retinal degeneration and decreased a-wave and b-wave amplitude in Zmpest24 KO mice, as compared with WT mice. Depletion of ZMPSTE24 led to significantly upregulation of inflammatory factors in retina, such as Casp1, CCL2, CCL3, ICAM1 and Mx1, which are involved in activation of interferon-gamma signaling and myeloid leukocyte activation.
Conclusions :
Our results demonstrate that ZMPSTE24 deficiency exacerbates LD-induced retinal degeneration and inflammation. Because prelamin A also exists in normal aging and promotes age-related diseases, this study provides novel information in retinal aging and age-related retinal diseases.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.