Ocular graft-versus-host-disease (GVHD) remains a significant clinical complication after allogeneic hematopoietic stem cell transplantation. Impaired visual function, pain, and other symptoms severely affect affected individuals’ quality of life. However, the diagnosis of and therapy for ocular GVHD involve a multidisciplinary approach and remain challenging for both hematologists and ophthalmologists, as there are no unified international criteria. Through an exploration of the complex pathogenesis of ocular GVHD, this review comprehensively summarizes the pathogenic mechanism, related tear biomarkers, and clinical characteristics of this disease. Novel therapies based on the mechanisms are also discussed to provide insights into the ocular GVHD treatment.

No in-depth systematic evidence is available for assessing retinoblastoma malignancy and eligibility for subsequent treatment. The Cochrane Library, EMBASE, PubMed, Web of Science, and China Biology Medicine databases were searched, and 16 studies comprising 718 retinoblastoma patients were included. Pooled odds ratios (ORs) and summary correlation coefficients (r) with 95% confidence intervals (CIs) in random-effects, fixed-effects or quality-effects models were calculated using Review Manager 5.3 and MetaXL. GO functional annotation and KEGG pathway analysis were performed using the GO and STRING databases. We observed significant associations between high levels of MMP-1 (OR, 4.21; 95% CI 1.86–9.54), MMP-2 (OR, 11.18; 95% CI 4.26–29.30), MMP-9 (OR, 10.41, 95% CI 4.26–25.47), and VEGF (OR, 8.09; 95% CI 4.03–16.20) with tumor invasion; high levels of MMP-1 (OR, 3.58; 95% CI 1.48–8.71), MMP-2 (OR, 2.96; 95% CI 1.32–6.64), MMP-9 (OR, 5.49; 95% CI 3.55–8.48) and VEGF (OR, 5.30; 95% CI 2.93–9.60) with poor differentiation; and overexpression of MMP-9 (OR, 5.17; 95% CI 2.85–9.38) with advanced clinical stages. Moreover, MMP-9 and VEGF expression were positively correlated (r, 0.61; 95% CI 0.38–0.77). Multiple GO terms were enriched associated with MMP-1, MMP-2, MMP-9 and VEGF, and they are closely associated with pathways, proteoglycans and microRNAs related to cancer. MMP-1, MMP-2, MMP-9 and VEGF play important roles in the development and progression of retinoblastoma. High levels of MMP-1, MMP-2, MMP-9 and VEGF are credible implications for increased malignancy, thus the need for more aggressive treatments.

Background: To study the effects of aerobic exercise (AE) on tear secretion and tear film stability in dry eye patients. Methods: This study consisted of two parts, each part included 3 groups, namely dry eye without AE group, dry eye with AE group and pre-clinical dry eye with AE group. In part 1, we studied the variations of Schirmer I test and six tear compositions before and after AE (34 eyes in each group). In part 2, we studied the variations of tear meniscus height, first and average non-invasive tear breakup time (F-NITBUT and A-NITBUT), lipid layer thickness, number of incomplete and complete blinks, partial blink rate (PBR) and visual acuity before and after AE (30 eyes in each group). Results: In dry eye with AE group, Schirmer I test at 0 min after AE increased significantly compared to baseline (P < 0.001), the oxidative stress marker 8-hydroxy-2′-deoxyguanosine after AE decreased significantly compared to baseline (P = 0.035, P = 0.045), F-NITBUT and A-NITBUT after AE prolonged significantly compared to baseline (P < 0.001, P = 0.007, P = 0.036; P < 0.001, P = 0.001, P = 0.044), number of incomplete blinks and PBR at 10 min after AE decreased significantly compared to baseline (P < 0.001; P < 0.001) while number of complete blinks increased significantly (P < 0.001). Besides, significant differences were also found between dry eye with AE group and dry eye without AE group at all above corresponding time point (P < 0.05). Conclusion: AE promotes tear secretion and improves tear film stability in dry eye patients. AE may be a potential treatment for dry eye. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000038673. Registered 27 September 2020,

Background: In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) exert major inhibitory effects on nerve regeneration: Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp). MAIs have two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Existing studies confirm that inhibiting NgR only exerted a modest disinhibitory effect in CNS. However, the inhibitory effects of PirB on nerve regeneration after binding to MAIs are controversial too. We aimed to further investigate the effect of PirB knockdown on the neuroprotection and axonal regeneration of retinal ganglion cells (RGCs) after optic nerve injury in rats. Methods: The differential expression of PirB in the retina was observed via immunofluorescence and western blotting after 1, 3, and 7 days of optic nerve injury (ONI). The retina was locally transfected with adeno-associated virus (AAV) PirB shRNA, then, the distribution of virus in tissues and cells was observed 21 days after AAV transfection to confirm the efficiency of PirB knockdown. Level of P-Stat3 and expressions of ciliary neurotrophic factor (CNTF) were detected via western blotting. RGCs were directly labeled with cholera toxin subunit B (CTB). The new axons of the optic nerve were specifically labeled with growth associated protein-43 (GAP43) via immunofluorescence. Flash visual evoked potential (FVEP) was used to detect the P1 and N1 latency, as well as N1-P1, P1-N2 amplitude to confirm visual function. Results: PirB expression in the retina was significantly increased after ONI. PirB knockdown was successful and significantly promoted P-Stat3 level and CNTF expression in the retina. PirB knockdown promoted the regeneration of optic nerve axons and improved the visual function indexes such as N1-P1 and P1-N2 amplitude. Conclusions: PirB is one of the key molecules that inhibit the regeneration of the optic nerve, and inhibition of PirB has an excellent effect on promoting nerve regeneration, which allows the use of PirB as a target molecule to promote functional recovery after ONI.