Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state
Abstract Neurodegeneration in glaucoma patients is clinically identified through longitudinal assessment of structure–function changes, including intraocular pressure, cup-to-disc ratios from fundus images, and optical coherence tomography imaging of the retinal nerve fiber layer. Use of human post-...
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BMC
2025-01-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-024-01880-2 |
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| author | Chuanxi Xiang VijayKrishna Raghunathan Yubin Qiu Manisha Mehta John T. Demirs Cynthia L. Grosskreutz Christopher W. Wilson Ganesh Prasanna |
| author_facet | Chuanxi Xiang VijayKrishna Raghunathan Yubin Qiu Manisha Mehta John T. Demirs Cynthia L. Grosskreutz Christopher W. Wilson Ganesh Prasanna |
| author_sort | Chuanxi Xiang |
| collection | DOAJ |
| description | Abstract Neurodegeneration in glaucoma patients is clinically identified through longitudinal assessment of structure–function changes, including intraocular pressure, cup-to-disc ratios from fundus images, and optical coherence tomography imaging of the retinal nerve fiber layer. Use of human post-mortem ocular tissue for basic research is rising in the glaucoma field, yet there are challenges in assessing disease stage and severity, since tissue donations with informed consent are often unaccompanied by detailed pre-mortem clinical information. Further, the interpretation of disease severity based solely on anatomical and morphological assessments by histology can be affected by differences in death-to-preservation time and tissue processing. These are difficult confounders that cannot be easily controlled. As pathogenesis and molecular mechanisms can vary depending on the stage and severity of glaucoma, there is a need for the field to maximize use of donated tissue to better understand the molecular mechanisms of glaucoma and develop new therapeutic hypotheses. Further, there is a lack of consensus around the molecular RNA and protein markers that can be used to classify glaucoma severity. Here, we describe a multiparametric grading system that combines structural measurements of the retinal nerve fiber layer with linear regression and principal component analyses of molecular markers of retinal ganglion cells and glia (RBPMS, NEFL, IBA1 and GFAP) to stratify post-mortem glaucoma eyes by the severity of disease. Our findings show that a quantitative grading approach can stratify post-mortem glaucoma samples with minimal clinical histories into at least three severity groups and suggest that this type of approach may be useful for researchers aiming to maximize insights derived from eye bank donor tissue. |
| format | Article |
| id | doaj-art-6a504356a82349be9776f0e13c377530 |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-6a504356a82349be9776f0e13c3775302025-01-12T12:43:56ZengBMCActa Neuropathologica Communications2051-59602025-01-0113111710.1186/s40478-024-01880-2Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease stateChuanxi Xiang0VijayKrishna Raghunathan1Yubin Qiu2Manisha Mehta3John T. Demirs4Cynthia L. Grosskreutz5Christopher W. Wilson6Ganesh Prasanna7Ophthalmology, Novartis Biomedical ResearchOphthalmology, Novartis Biomedical ResearchOphthalmology, Novartis Biomedical ResearchOphthalmology, Novartis Biomedical ResearchOphthalmology, Novartis Biomedical ResearchOphthalmology, Novartis Biomedical ResearchOphthalmology, Novartis Biomedical ResearchOphthalmology, Novartis Biomedical ResearchAbstract Neurodegeneration in glaucoma patients is clinically identified through longitudinal assessment of structure–function changes, including intraocular pressure, cup-to-disc ratios from fundus images, and optical coherence tomography imaging of the retinal nerve fiber layer. Use of human post-mortem ocular tissue for basic research is rising in the glaucoma field, yet there are challenges in assessing disease stage and severity, since tissue donations with informed consent are often unaccompanied by detailed pre-mortem clinical information. Further, the interpretation of disease severity based solely on anatomical and morphological assessments by histology can be affected by differences in death-to-preservation time and tissue processing. These are difficult confounders that cannot be easily controlled. As pathogenesis and molecular mechanisms can vary depending on the stage and severity of glaucoma, there is a need for the field to maximize use of donated tissue to better understand the molecular mechanisms of glaucoma and develop new therapeutic hypotheses. Further, there is a lack of consensus around the molecular RNA and protein markers that can be used to classify glaucoma severity. Here, we describe a multiparametric grading system that combines structural measurements of the retinal nerve fiber layer with linear regression and principal component analyses of molecular markers of retinal ganglion cells and glia (RBPMS, NEFL, IBA1 and GFAP) to stratify post-mortem glaucoma eyes by the severity of disease. Our findings show that a quantitative grading approach can stratify post-mortem glaucoma samples with minimal clinical histories into at least three severity groups and suggest that this type of approach may be useful for researchers aiming to maximize insights derived from eye bank donor tissue.https://doi.org/10.1186/s40478-024-01880-2GlaucomaRetinal nerve fiber layerPathology gradingNeurodegenerationHistologyMultivariate analysis |
| spellingShingle | Chuanxi Xiang VijayKrishna Raghunathan Yubin Qiu Manisha Mehta John T. Demirs Cynthia L. Grosskreutz Christopher W. Wilson Ganesh Prasanna Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state Acta Neuropathologica Communications Glaucoma Retinal nerve fiber layer Pathology grading Neurodegeneration Histology Multivariate analysis |
| title | Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state |
| title_full | Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state |
| title_fullStr | Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state |
| title_full_unstemmed | Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state |
| title_short | Multiparametric grading of glaucoma severity by histopathology can enable post-mortem substratification of disease state |
| title_sort | multiparametric grading of glaucoma severity by histopathology can enable post mortem substratification of disease state |
| topic | Glaucoma Retinal nerve fiber layer Pathology grading Neurodegeneration Histology Multivariate analysis |
| url | https://doi.org/10.1186/s40478-024-01880-2 |
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