Abstract
Purpose :
To assess the photoreceptor cell death and leukocyte recruitment in widely used retinal detachment (RD) models in mice.
Methods :
We performed a literature search to investigate the RD models in mice over the past 20 years (PubMed search terms: “retinal detachment” and “mouse”). Following, we induced an experimental RD in mice using the two most widely used approaches to investigate model divergences. Briefly, 1% sodium hyaluronate was injected into the subretinal space via the transvitreal (TV) and transscleral (TS) approaches in 8-week-old C57BL/6J and Cx3Cr1-GFP Ccr2-RFP mice. We analyzed photoreceptor survival at day 7 after RD in retinal cryosections stained with DAPI. We quantitated leukocyte infiltration (CD11b+, CX3CR1+, and CCR2+ cells) by immunofluorescence in retinal wholemounts in the detached retina.
Results :
We found 192 PubMed results matching our criteria: 45 TS approach, 22 TV approach, and 125 were excluded due to lack of experimental data or unclear methodological approach (Figure 1). Our experimental data shows that both TV and TS models induced significant photoreceptor cell death in the detached retina. At 7 days following RD, the photoreceptor count was 920.58 ± 34.41 in the TS model and 1067.42 ± 32.49 in the TV model (p < 0.001 vs. attached retina, both groups, Student's t-test, n = 4). However, the TS model induced a more pronounced cell death than the TV model in the detached retina (p = 0.019, Student's t-test, n = 4). There were no significant differences in the outer nuclear layer/inner nuclear layer ratios (p = 0.542, Student's t-test, n = 7-10). Regarding the leukocyte infiltration, we observed on day 1 after RD, a higher number of CD11b+ CCR2+ cells in the TS model (99.17 ± 24.34 cells) compared to the TV model (30.57 ± 11.33), with statistical significance (p = 0.021, t-test, n = 3).
Conclusions :
Over the past few years, the TS approach has been the more commonly used model to induce RD in mice. Our results suggest that the TS model may induce more pronounced photoreceptor cell death, when compared to the TV model. Additionally, the TS model results in a more significant early immune cell infiltration in the detached retina. This data should raise awareness of the implications of experimental model selection on photoreceptor cell death analysis.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.