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Intrinsic Expression of Coagulation Factors and Protease Activated Receptor 1 (PAR1) in Photoreceptors and Inner Retinal Layers.

ABSTRACT: The aim of this study was to characterize the distribution of the thrombin receptor, protease activated receptor 1 (PAR1), in the neuroretina. Neuroretina samples of wild-type C57BL/6J and PAR1^-/- mice were processed for indirect immunofluorescence and Western blot analysis. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to determine mRNA expression of coagulation Factor X (FX), prothrombin (PT), and PAR1 in the isolated neuroretina. Thrombin activity following KCl depolarization was assessed in mouse neuroretinas ex vivo. PAR1 staining was observed in the retinal ganglion cells, inner nuclear layer cells, and photoreceptors in mouse retinal cross sections by indirect immunofluorescence. PAR1 co-localized with rhodopsin in rod outer segments but was not expressed in cone outer segments. Western blot analysis confirmed PAR1 expression in the neuroretina. Factor X, prothrombin, and PAR1 mRNA expression was detected in isolated neuroretinas. Thrombin activity was elevated by nearly four-fold in mouse neuroretinas following KCl depolarization (0.012 vs. 0.044 mu/mL, p = 0.0497). The intrinsic expression of coagulation factors in the isolated neuroretina together with a functional increase in thrombin activity following KCl depolarization may suggest a role for the PAR1/thrombin pathway in retinal function.

SUBMITTER: Goldberg Z

PROVIDER: S-EPMC8778890 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo determine whether disorganization of retinal inner layers (DRIL) on optical coherence tomography (OCT) is associated with ischemia on ultra-widefield fluorescein angiography (UWFFA) and with visual outcomes in eyes with acute, treatment-naïve central retinal vein occlusion (CRVO).DesignRetrospective, single-institution, longitudinal cohort study.ParticipantsTwenty-five consecutive patients with treatment-naïve CRVO and ≥ 1 year follow-up.MethodsTwo independent masked graders evaluated the extent of DRIL, ellipsoid zone disruption, external limiting membrane disruption, and other OCT parameters at the baseline, 6- month, 12-month, and final visits. Baseline UWFFA images were assessed for ischemic index values and foveal avascular zone (FAZ) enlargement.Main outcome measuresAssociations of DRIL with UWFFA findings and clinical outcomes including corrected visual acuity (VA).ResultsThe median time to final follow-up was 24 months (range 12.1 - 43.9 months). Median DRIL extent at baseline was 765 µm (range 0 - 1000 µm). Eighteen of 25 eyes (72%) had some degree of DRIL at baseline, and 20 of 25 eyes (80%) had cystoid macular edema (CME). Neither the presence nor extent of DRIL at baseline was associated with presenting VA. In a cross-sectional analysis of each visit, extent of DRIL correlated with worse VA at both the 6-month (ρ = 0.656; p = 0.001) and final (ρ = 0.509; p = 0.016) visits. At final follow-up, DRIL extent was the OCT parameter most strongly correlated with baseline ischemic index (ρ = 0.418; p = 0.047) and baseline enlarged FAZ (p = 0.057) on UWFFA. On multivariate regression analysis, DRIL extent at final follow-up was the only OCT parameter associated with worse VA (p = 0.013) and remained significant when accounting for CME as a potential confounder.ConclusionsExtent of DRIL was not associated with presenting VA in treatment-naïve eyes with acute CRVO. Following six months of follow-up however, DRIL extent correlated with worse VA and was predictive of worse VA throughout more than 2 years of follow-up. Ischemic features on UWFFA at baseline are predictive of the extent of DRIL development at final follow-up.

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Intrinsic Expression of Coagulation Factors and Protease Activated Receptor 1 (PAR1) in Photoreceptors and Inner Retinal Layers.

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