transpupillary-guided-trans-scleral-transplantation-subretinal-grafts

Transpupillary-Guided Trans-Scleral Transplantation of Subretinal Grafts in a Retinal Degeneration Mouse Model

Transplantation of photoreceptor cells and retinal pigment&#160;epithelial (RPE) cells provide a potential therapy for retinal degeneration diseases. ...

Johns Hopkins University School of Medicine

The use of Specific Pathogen Free (SPF) eggs in combination with RCAS retrovirus, a member of the Avian Sarcoma-Leukosis Virus (ASLV) family, is of standard practice to study gene function and development. SPF eggs are certified free of infection by specific pathogen viruses of either exogenous or endogenous origin, including those belonging to the ASLV family. Based on this, SPF embryos are considered to be free of ASLV viral protein expression, and consequently in developmental research studies RCAS infected cells are routinely identified by immunohistochemistry against the ASLV viral proteins p19 and p27. Contrary to this generally accepted notion, observations in our laboratory suggested that certified SPF chicken embryos may endogenously express ASLV viral proteins p19 and p27. Since these observations may have significant implications for the developmental research field we further investigated this possibility.

Endogenous expression of ASLV viral proteins in specific pathogen free chicken embryos: relevance for the developmental biology research field.

Short-term improvements in retinal anatomy are known to occur in preclinical models of photoreceptor transplantation. However, correlative changes over the long term are poorly understood. We aimed to develop a quantifiable imaging biomarker grading scheme, using noninvasive multimodal confocal scanning laser ophthalmoscopy (cSLO) imaging, to enable serial evaluation of photoreceptor transplantation over the long term.

Quantifiable In Vivo Imaging Biomarkers of Retinal Regeneration by Photoreceptor Cell Transplantation.

Cone photoreceptor transplantation is a potential treatment for macular diseases. The optimal conditions for cone transplantation are poorly understood, partly because of the scarcity of cones in donor mice. To facilitate allogeneic cone photoreceptor transplantation studies in mice, we aimed to create and characterize a donor mouse model containing a cone-rich retina with a cone-specific enhanced green fluorescent protein (EGFP) reporter.

Characterization and allogeneic transplantation of a novel transgenic cone-rich donor mouse line.

Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases.

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Proliferative vitreoretinopathy (PVR) is the most common cause of failure of retinal reattachment surgery, and the molecular changes leading to this aberrant wound healing process are currently unknown. Our ultimate goal is to study PVR pathogenesis by employing single-cell transcriptomics to dissect cellular heterogeneity.

Comparative Analysis of Single-cell and Single-nucleus RNA-sequencing in a Rabbit Model of Retinal Detachment-related Proliferative Vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is the most common cause of failure of surgically repaired rhegmatogenous retinal detachment (RRD). Chemically induced and cell injection PVR models do not fully simulate the clinical characteristics of PVR in the post-RRD context. There is an unmet need for translational models in which to study mechanisms and treatments specific to RRD-PVR.

Article	Year
Endogenous expression of ASLV viral proteins in specific pathogen free chicken embryos: relevance for the developmental biology research field. BMC developmental biology\| PubMed ID: 20955591	2010
Quantifiable In Vivo Imaging Biomarkers of Retinal Regeneration by Photoreceptor Cell Transplantation. Translational vision science & technology\| PubMed ID: 32832212	2020
Characterization and allogeneic transplantation of a novel transgenic cone-rich donor mouse line. Experimental eye research\| PubMed ID: 34343570	2021
Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin. Stem cell reports\| PubMed ID: 37163980	2023
Comparative Analysis of Single-cell and Single-nucleus RNA-sequencing in a Rabbit Model of Retinal Detachment-related Proliferative Vitreoretinopathy. Ophthalmology science\| PubMed ID: 37496518	2023
Transition to Chronic Fibrosis in an Animal Model of Retinal Detachment With Features of Proliferative Vitreoretinopathy. Investigative ophthalmology & visual science\| PubMed ID: 38153753	2023

Minda M. McNally

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