Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice
Abstract Subretinal injections provide direct access to photoreceptors and RPE, which is crucial for the delivery of gene therapy and neuroprotective approaches. To access the subretinal space, transvitreal (TV) and transscleral (TS) subretinal injections have been widely used in humans and animal m...
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BMC
2025-02-01
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| Series: | Journal of Inflammation |
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| Online Access: | https://doi.org/10.1186/s12950-025-00433-1 |
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| author | Daniel E. Maidana Sara Pastor Puente Catherine Wang Shivam Chandra Lucia Gonzalez-Buendia Eleftherios Paschalis Ilios Andrius Kazlauskas Demetrios G. Vavvas |
| author_facet | Daniel E. Maidana Sara Pastor Puente Catherine Wang Shivam Chandra Lucia Gonzalez-Buendia Eleftherios Paschalis Ilios Andrius Kazlauskas Demetrios G. Vavvas |
| author_sort | Daniel E. Maidana |
| collection | DOAJ |
| description | Abstract Subretinal injections provide direct access to photoreceptors and RPE, which is crucial for the delivery of gene therapy and neuroprotective approaches. To access the subretinal space, transvitreal (TV) and transscleral (TS) subretinal injections have been widely used in humans and animal models. In this work, we investigated recent trends and outcomes of utilizing TV and TS subretinal models of retinal detachment (RD). A literature review revealed an increasing utilization of both models over the past two decades, with TS emerging as the predominant model since 2012. Subretinal injection in CX3CR1 + /GFP CCR2 + /RFP mice revealed early inflammatory responses, with TS injections inducing higher infiltration of CD11b + CCR2 + cells compared to TV. Further leukocyte immunophenotyping indicated divergent infiltration patterns, with the TS approach exhibiting higher proportions of neutrophils and macrophages/microglia-like cells, while the TV injections had higher CD45hi CD11b + Ly6G- Ly6C + infiltration. Notably, late-stage analysis demonstrates higher photoreceptor cell death in the TS approach, paralleled by increased subretinal infiltration of CD11b + cells. Both models showed significant reactive gliosis, suggesting comparable late-stage wound healing responses. These findings underscore the utility of these approaches for subretinal delivery, offering insights into their distinctive leukocyte infiltration and late-stage tissue responses. |
| format | Article |
| id | doaj-art-1ea2d2089cac4e529d8c90c946cddf8b |
| institution | Kabale University |
| issn | 1476-9255 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj-art-1ea2d2089cac4e529d8c90c946cddf8b2025-02-09T12:12:09ZengBMCJournal of Inflammation1476-92552025-02-012211910.1186/s12950-025-00433-1Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in miceDaniel E. Maidana0Sara Pastor Puente1Catherine Wang2Shivam Chandra3Lucia Gonzalez-Buendia4Eleftherios Paschalis Ilios5Andrius Kazlauskas6Demetrios G. Vavvas7Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at ChicagoDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at ChicagoDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at ChicagoDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at ChicagoRetina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical SchoolRetina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical SchoolDepartment of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at ChicagoRetina Service, Angiogenesis Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical SchoolAbstract Subretinal injections provide direct access to photoreceptors and RPE, which is crucial for the delivery of gene therapy and neuroprotective approaches. To access the subretinal space, transvitreal (TV) and transscleral (TS) subretinal injections have been widely used in humans and animal models. In this work, we investigated recent trends and outcomes of utilizing TV and TS subretinal models of retinal detachment (RD). A literature review revealed an increasing utilization of both models over the past two decades, with TS emerging as the predominant model since 2012. Subretinal injection in CX3CR1 + /GFP CCR2 + /RFP mice revealed early inflammatory responses, with TS injections inducing higher infiltration of CD11b + CCR2 + cells compared to TV. Further leukocyte immunophenotyping indicated divergent infiltration patterns, with the TS approach exhibiting higher proportions of neutrophils and macrophages/microglia-like cells, while the TV injections had higher CD45hi CD11b + Ly6G- Ly6C + infiltration. Notably, late-stage analysis demonstrates higher photoreceptor cell death in the TS approach, paralleled by increased subretinal infiltration of CD11b + cells. Both models showed significant reactive gliosis, suggesting comparable late-stage wound healing responses. These findings underscore the utility of these approaches for subretinal delivery, offering insights into their distinctive leukocyte infiltration and late-stage tissue responses.https://doi.org/10.1186/s12950-025-00433-1Retinal detachmentOuter nuclear layerCD11bCX3CR1CCR2Gliosis |
| spellingShingle | Daniel E. Maidana Sara Pastor Puente Catherine Wang Shivam Chandra Lucia Gonzalez-Buendia Eleftherios Paschalis Ilios Andrius Kazlauskas Demetrios G. Vavvas Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice Journal of Inflammation Retinal detachment Outer nuclear layer CD11b CX3CR1 CCR2 Gliosis |
| title | Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice |
| title_full | Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice |
| title_fullStr | Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice |
| title_full_unstemmed | Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice |
| title_short | Divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice |
| title_sort | divergence in photoreceptor cell death and neuroinflammation in transvitreal and transscleral subretinal delivery in mice |
| topic | Retinal detachment Outer nuclear layer CD11b CX3CR1 CCR2 Gliosis |
| url | https://doi.org/10.1186/s12950-025-00433-1 |
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