Utility of the DHFR-based destabilizing domain across mouse models of retinal degeneration and aging

Peng, Hui; Ramadurgum, Prerana; Woodard, DaNae R; Daniel, Steffi; Nakahara, Emi; Renwick, Marian; Aredo, Bogale; Datta, Shyamtanu; Chen, Bin; Ufret-Vincenty, Rafael; Hulleman, John D.

doi:10.1016/j.isci.2022.104206

Cited by 1 publication

(2 citation statements)

References 79 publications

(101 reference statements)

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“…However, to our knowledge, this report is the first that implicates Muller cells as playing an important role in mouse retinal recovery from a mild light injury. We have reported previously retinal recovery from light injury supported by structural and functional analyses 33 , 34 , 43 , 44 and now we are starting to understand the mechanisms behind this recovery process.…”

Section: Discussionmentioning

confidence: 87%

“…The flow chart presented in Figure 1 shows the protocols and steps used in this work starting from the application of light injury to the analysis of single cell RNA-seq (scRNA-seq). Based on our prior studies, 33 , 34 , 43 , 44 we had determined that the FCD-LIRD model led to retinal light injury that could modulated be easily by modifying the intensity of the light stimulus. In this model, maximal injury as seen on fundus photos and OCT can be seen at approximately day 5 after injury.…”

Section: Resultsmentioning

confidence: 99%

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Single Cell RNA Sequencing Analysis of Mouse Retina Identifies a Subpopulation of Muller Glia Involved in Retinal Recovery From Injury in the FCD-LIRD Model

Aredo

Kumar

Chen

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose Although retinal light injury models have been useful in understanding aspects of retinal degeneration and retinal oxidative stress, information on retinal recovery from oxidative/photoinflammatory retinal injury is scarce. The fundus camera-delivered light-induced retinal degeneration model is a simple and reproducible retinal light injury model developed to recapitulate not only the retinal degeneration aspect, but also the retinal recovery from injury. In this study, we used the fundus camera-delivered light-induced retinal degeneration model to perform cell type-specific analyses of the acute and subacute retinal responses to light injury. Methods C57BL/6J eyes were collected before or after light injury (4 hours, 48 hours, and day 5). Retina samples were processed into single-cell suspensions. Droplet-based encapsulation of single cells was performed to generate libraries for sequencing. Results Gene expression analysis generated 23 clusters encompassing all known major retinal cell populations. Using unbiased analyses, we identified genes and pathways that were significantly altered in each cell type after light injury, including some cellular processes suggestive of activation of pathways for retinal recovery (e.g., synaptogenesis signaling, ephrin receptor signaling, and Reelin signaling in neurons). More importantly, our data show that a subpopulation of Muller glia cells may play an important role in the cellular recovery process. Conclusions This work identifies acute and subacute cell type-specific responses to retinal photo-oxidative injury. A subpopulation of Muller glia seems to initiate the cellular recovery process. A better understanding of these responses may be helpful in identifying therapeutic approaches to minimize retinal damage and maximize recovery after exposure to injury.

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