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Using\n                      <jats:italic>rd10<\/jats:italic>\n                      mice, which mirror the human condition, we examined its disease progression. Rods deteriorate by postnatal day (P) 45, followed by cone degeneration, with most photoreceptors lost by P180. Until then, retinal ganglion cells (RGCs) remain light\u2010responsive under photopic conditions, despite extensive outer retinal remodelling. However, it is still unknown if distinct functional RGC types alter their activity or are even lost during disease progression. Here, we asked if and how the response diversity of functional RGC types changes with\n                      <jats:italic>rd10<\/jats:italic>\n                      disease progression. At P30, we identified all functional wild\u2010type RGC types also in\n                      <jats:italic>rd10<\/jats:italic>\n                      retinae, suggesting that at this early degenerative stage, the full breadth of retinal output is still present. Remarkably, we found that the fractions of functional types changed throughout progressing degeneration between\n                      <jats:italic>rd10<\/jats:italic>\n                      and wild\u2010type: responses of RGCs with \u2018Off\u2019\u2010components (\u2018Off\u2019 and \u2018On\u2013Off\u2019 RGCs) were more vulnerable than \u2018On\u2019\u2010cells, with \u2018Fast On\u2019 types being the most resilient. Notably, direction\u2010selective RGCs appeared to be more vulnerable than orientation\u2010selective RGCs. In summary, we found differences in resilience of response types (from resilient to vulnerable): \u2018Uncertain\u2019 &gt; \u2018Fast On\u2019 &gt; \u2018Slow On\u2019 &gt; \u2018On\u2013Off\u2019 &gt; \u2018Off\u2019. Taken together, our results suggest that\n                      <jats:italic>rd10<\/jats:italic>\n                      photoreceptor degeneration has heterogeneous effects on functional RGC types, with distinct sets of types losing their characteristic light responses earlier than others. This differential susceptibility of RGC circuits may be of relevance for future neuroprotective therapeutic strategies.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16546-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Retinitis pigmentosa is a hereditary disease causing progressive degeneration of rod and cone photoreceptors, with no effective therapies; it can be investigated using mutant mouse models, like\n                            <jats:italic>rd10<\/jats:italic>\n                            , that mirror the human condition.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Recent studies found that retinal ganglion cells (RGCs) in\n                            <jats:italic>rd10<\/jats:italic>\n                            remain light\u2010responsive, despite extensive loss of photoreceptors and outer retinal remodelling; however, specific RGC types still may change or even lose their functional response profile during early degeneration.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Using two\u2010photon calcium imaging, we assessed if and how the light\u2010evoked activity of RGCs, and, hence, the retinal output to the brain, differs during the disease progression in\n                            <jats:italic>rd10<\/jats:italic>\n                            compared to wild\u2010type mice.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We found differences in the resilience of functional RGC types: generally, \u2018On\u2019\u2010types were more resilient than \u2018On\u2013Off\u2019 or especially \u2018Off\u2019 types.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Our data suggest that interventions may be more effective in the \u2018On\u2019 pathways, which turned out to be more resilient in\n                            <jats:italic>rd10<\/jats:italic>\n                            .\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp287643","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T08:07:55Z","timestamp":1739261275000},"page":"6599-6621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Photoreceptor degeneration has heterogeneous effects on functional retinal ganglion cell types"],"prefix":"10.1113","volume":"603","author":[{"given":"Nadine","family":"Dyszkant","sequence":"first","affiliation":[{"name":"Institute for Ophthalmic Research University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Werner Reichardt Centre for Integrative Neuroscience University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Graduate Training Centre of 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