Dataset Information

Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina

ABSTRACT: Chronic ocular inflammation is associated with many retinal degenerative diseases that result in vision loss. The immune-privileged environment and complex organization of retinal tissue allow for the retina’s essential role in visual function processes, yet confound inquiries into cell-specific inflammatory effects that lead to retinal dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in many retinal cell populations and has been implicated in retinal immune regulation. However, the direction (i.e., promotion or inhibition) in which Cav1 regulates inflammatory processes in the retina (as well as in other tissues) remains unclear. Previously, we showed that global-Cav1 depletion in the retina paradoxically resulted in reduced retinal inflammatory cytokine production with concurrent elevated retinal immune cell infiltration. We hypothesized that our previous results could be explained by cell-specific Cav1 functions in the retina. Here, we utilized our Chx10 (visual system homeobox 2)-Cre knockout model to deplete Cav1 specifically in the neural retinal (NR) compartment in order to clarify the role of neural retinal-specific Cav1 (NR-Cav1) in the retinal immune response to intravitreal LPS (lipopolysaccharide) challenge. Our data support that neural retinal-derived Cav1 promotes retinal tissue inflammation as Chx10-mediated Cav1 depletion was sufficient to suppress both retinal cytokine production and immune cell infiltration following inflammatory stimulation. Additionally, we identify Traf3 (tumor necrosis factor (TNF) receptor-associated factor 3) as a highly expressed potential immune modulator in retinal tissue that is upregulated with NR-Cav1 depletion. Furthermore, this study highlights the importance for understanding the role of Cav1 (and other proteins) in cell-specific contexts.

INSTRUMENT(S): LTQ Orbitrap XL

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Retina

DISEASE(S): Inflammation

SUBMITTER: Sandra Sagmeister

LAB HEAD: Stefanie M. Hauck

PROVIDER: PXD016872 | Pride | 2021-09-08

REPOSITORIES: Pride

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Publications

Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina.

Gurley Jami M JM Gmyrek Grzegorz B GB McClellan Mark E ME Hargis Elizabeth A EA Hauck Stefanie M SM Dozmorov Mikhail G MG Wren Jonathan D JD Carr Daniel J J DJJ Elliott Michael H MH

Investigative ophthalmology & visual science 20201001 12

<h4>Purpose</h4>The immune-privileged environment and complex organization of retinal tissue support the retina's essential role in visual function, yet confound inquiries into cell-specific inflammatory effects that lead to dysfunction and degeneration. Caveolin-1 (Cav1) is an integral membrane protein expressed in several retinal cell types and is implicated in immune regulation. However, whether Cav1 promotes or inhibits inflammatory processes in the retina (as well as in other tissues) remai ...[more]

PMID: 33079993

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Project description:The vertebrate retina uses diverse neuronal cell types arrayed into complex neural circuits to extract, process and relay information from the visual scene to the higher order processing centers of the brain. Amacrine cells, a diverse class of inhibitory interneurons, are thought to mediate the majority of the processing of the visual signal that occurs within the retina. Despite morphological characterization, the number of known molecular markers of amacrine cell types is still much smaller than the 26 morphological types that have been identified. Furthermore, it is not known how this diversity arises during development. Here, we have combined in vivo genetic labeling and single cell genome-wide expression profiling to: 1) Identify specific molecular types of amacrine cells; 2) Demonstrate the molecular diversity of the amacrine cell class. It is difficult to identify new markers of amacrine cells, due to the fact that they only comprise a small percentage of the total cells in the retina. Additionally, given that there are at least 26 distinct types of amacrine cells, population based approaches fail to achieve the precision necessary to discover markers of each type. To facilitate the identification of new markers for different amacrine cell classes and to more fully characterize the molecular signatures of these classes, we isolated single amacrine cells. To accomplish this goal, we introduced genetic reporters (pNdrg4::GFP or pSynapsin::GFP) into the developing retina (P0) by either in vivo or ex vivo electroporation. These reporters were observed to label morphologically distinct sets of amacrine cells at the different timepoints harvested in this study. Electroporated retinas were then dissociated at different time points and single retinal amacrine cells were isolated by virtue of their GFP expression and placed in tubes containing lysis buffer. Then, their mRNAs were reverse transcribed, and the resulting cDNAs were PCR amplified for 35 cycles. Labeled cDNA samples were hybridized to Affymetrix 430 2.0 microarrays and the data was normalized using MAS5.0 software.

Dataset Information

Neuroretinal-derived caveolin-1 promotes endotoxin-induced inflammation in the murine retina

Publications

Neuroretinal-Derived Caveolin-1 Promotes Endotoxin-Induced Inflammation in the Murine Retina.

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