UVA induces retinal photoreceptor cell death via receptor interacting protein 3 kinase mediated necroptosis

Ultraviolet light A (UVA) is the only UV light that reaches the retina and can cause indirect damage to DNA via absorption of photons by non-DNA chromophores. Previous studies demonstrate that UVA generates reactive oxygen species (ROS) and leads to programmed cell death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor interacting protein 1 and 3 (RIPK1 and RIPK3) kinases, key signaling molecules of PCD, in UVA-induced photoreceptor injury using in vitro and ex vivo models. UVA irradiation activated RIPK3 but not RIPK1 and mediated necroptosis through MLKL that lie downstream of RIPK3 and induced apoptosis through increased oxidative stress. Moreover, RIPK3 but not RIPK1 inhibition suppresses UVA-induced cell death along with the downregulation of MLKL and attenuates the levels of oxidative stress and DNA fragmentation. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced necroptosis cell death in photoreceptors and highlight RIPK3 potential as a neuroprotective target.This work was supported by the Yeatts Family Foundation (D.G.V.); Monte J. Wallace (D.G.V.); 2013 Macula Society Research Grant Award (to D.G.V.); a Physician Scientist Award (to D.G.V.); unrestricted grant from the Research to Prevent Blindness Foundation (to J.W.M. and D.G.V.); National Eye Institute (NEI) R21EY023079-01/A1 (to D.G.V.); NEI Grant EY014104 (Massachusetts Eye and Ear Infirmary Core Grant) (to D.G.V.); Loeffler Family Fund (D.G.V.); R01EY025362-01 (to D.G.V.); ARI Young Investigator Award (to D.G.V.); Foundation Lions Eye Research Fund (D.G.V.); NIH NEI Core Grant P30EY003790 (to D.G.V.); Loeffler Family Fund (to D.G.V.); ARI Young Investigator Award (to D.G.V.). Shenzhen Science and Technology Program (Grant No. JCYJ20220530153607015); Shenzhen Science and Technology Program (Grant No. JCYJ20220531094004010); Shenzhen-Hong Kong Co-financing Project (Grant No. SGDX20190920110403741); Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515012326); Shenzhen Science and Technology Program (Grant No. JSGG20201102174200001); Shenzhen Key Medical Discipline Construction Fund (No. SZXK038); Sanming Project of Medicine in Shenzhen (No. SZSM202011015); Shenzhen Fund for Guangdong Provincial High level Clinical Key Specialties (No. SZGSP014); National Natural Science Foundation of China (No. 82271103)

Statokinetic Dissociation (Riddoch Phenomenon) in a Patient with Homonymous Hemianopsia as the First Sign of Posterior Cortical Atrophy

We report a 60-year-old woman with posterior cortical atrophy (PCA) who presented with left homonymous hemianopsia persisting for 5 years; the patient’s condition was observed using static, but not kinetic, perimetry. This statokinetic dissociation of hemianopsia, which is often called Riddoch syndrome, might have been caused by a dysfunction of the right primary visual and visual association cortices, representing a functional imbalance within a disturbed visual cortex. In patients with PCA and visual field defects, both static and kinetic perimetry may be useful for understanding the extent of degeneration in the visual cortex, in addition to examinations of unilateral neglect