Age-Related RPE changes in Wildtype C57BL/6J Mice between 2 and 32 Months.

TitleAge-Related RPE changes in Wildtype C57BL/6J Mice between 2 and 32 Months.
Publication TypeJournal Article
Year of Publication2024
AuthorsShelton, DA, Gefke, I, Summers, V, Kim, Y-K, Yu, H, Getz, Y, Ferdous, S, Donaldson, K, Liao, K, Papania, JT, Chrenek, MA, Boatright, JH, Nickerson, JM
Date Published2024 Feb 01

PURPOSE: This study provides a systematic evaluation of age-related changes in RPE cell structure and function using a morphometric approach. We aim to better capture nuanced predictive changes in cell heterogeneity that reflect loss of RPE integrity during normal aging. Using C57BL6/J mice ranging from P60-P730, we sought to evaluate how regional changes in RPE shape reflect incremental losses in RPE cell function with advancing age. We hypothesize that tracking global morphological changes in RPE is predictive of functional defects over time.

METHODS: We tested three groups of C57BL/6J mice (young: P60-180; Middle-aged: P365-729; aged: 730+) for function and structural defects using electroretinograms, immunofluorescence, and phagocytosis assays.

RESULTS: The largest changes in RPE morphology were evident between the young and aged groups, while the middle-aged group exhibited smaller but notable region-specific differences. We observed a 1.9-fold increase in cytoplasmic alpha-catenin expression specifically in the central-medial region of the eye between the young and aged group. There was an 8-fold increase in subretinal, IBA-1-positive immune cell recruitment and a significant decrease in visual function in aged mice compared to young mice. Functional defects in the RPE corroborated by changes in RPE phagocytotic capacity.

CONCLUSIONS: The marked increase of cytoplasmic alpha-catenin expression and subretinal immune cell deposition, and decreased visual output coincide with regional changes in RPE cell morphometrics when stratified by age. These cumulative changes in the RPE morphology showed predictive regional patterns of stress associated with loss of RPE integrity.

Alternate JournalbioRxiv
PubMed ID38352604
PubMed Central IDPMC10862734
Grant ListR01 EY028859 / EY / NEI NIH HHS / United States
P30 EY006360 / EY / NEI NIH HHS / United States
U01 CA242936 / CA / NCI NIH HHS / United States
I21 RX001924 / RX / RRD VA / United States
R01 DC009246 / DC / NIDCD NIH HHS / United States
T32 EY007092 / EY / NEI NIH HHS / United States
R01 EY021592 / EY / NEI NIH HHS / United States
R01 EY028450 / EY / NEI NIH HHS / United States
I01 RX002806 / RX / RRD VA / United States
T32 GM008490 / GM / NIGMS NIH HHS / United States