Syphilitic uveitis in HIV-positive patients: report of a case series, treatment outcomes, and comprehensive review of the literature.

AIM: To report the clinical characteristics, treatment and outcomes of active syphilitic uveitis in human immunodeficiency virus (HIV) positive patients and compare them with the previously published data. METHODS: Retrospective analysis of the case series from an infectious disease center in southern China was conducted. Comprehensive review of previously published cases of HIV positive syphilitic uveitis was conducted using the PubMed and Web of Science databases and the references listed in the identified articles. RESULTS: Twelve HIV positive patients with active syphilitic uveitis were collected. All were male, with age of 36.3y (range 27 to 53y). Five (41.7%) had a history of syphilis, and three of them had received anti-syphilis treatment. Ocular manifestations included corneal epithelial defect (13%), complicated cataract (17.4%), vitreous opacity (82.6%), optic disc edema (26.1%), macular edema (30.4%), neuro-retinitis (43.5%), and retinal hemorrhage (26.1%). After standardized syphilitic treatment, intraocular inflammation was reduced and vision improved in all cases. The literature review summarizes 105 previously reported cases of HIV positive syphilitic uveitis. High serum rapid plasma regain (RPR) titers may be associated with severe uveitis and poor vision. Treatment with penicillin, ceftriaxone sodium, or penicillin plus benzylpenicillin instead of using benzylpenicillin alone can significantly improve best-corrected visual acuity (BCVA) in HIV positive ocular syphilis patients. CONCLUSION: For HIV positive syphilitic uveitis patients, prompt diagnosis and appropriate treatment and follow-up are paramount. In our series, the clinical manifestations are diverse. Syphilis patients treated by penicillin G or long-acting penicillin before may still develop syphilitic uveitis. Patients who relapse after long-term penicillin treatment can still benefit from penicillin G.

The correlation between human leucocyte antigen amino acid residue matching before keratoplasty and postoperative rejection: a systematic review and meta-analysis.

BACKGROUND: At present, corneal transplantation has become the main surgical method for infectious keratitis. However, the rejection of corneal graft after operation leads to graft opacity, which is an important reason for the failure of transplantation. There is no unified conclusion whether the rejection can be reduced by matching human leucocyte antigen (HLA) before operation. The purpose of this meta-analysis is to explore the correlation between HLA locus matching and corneal transplantation rejection, so as to provide evidence-based medical evidence for clinical corneal transplantation in the treatment of infectious keratitis. METHODS: Search English databases, such as PubMed, Medline, Embase and Evidence-based Medicine Library by computer; Chinese databases, such as China Biomedical Literature Database, China Knowledge Network (CNKI) database, Wanfang database, Weipu database, and Google Academic database. According to Cochrane Handbook 5.0 risk assessment table, two researchers made random sequence random allocation method, blind method, allocation scheme hiding, integrity of data results and quality score of research results. The bias risk evaluation of Rev Man 5.3 software was used to evaluate the risk bias of the references. RESULTS: A total of 5 literatures were included, and 725 eyes underwent penetrating keratoplasty, all of which were randomized controlled trials (RCTs). The quality of the included articles was medium to high quality. A meta-analysis of four HLA-A matching articles showed odds ratio (OR) =0.28, 95% confidential interval (CI): (0.15, 0.51), significance test Z=4.08, P<0.0001, and the difference was statistically significant. Meta-analysis was performed on four HLA-B matching articles and showed OR =0.50, 95% CI: (0.27, 0.89), significance test Z=2.33, P=0.02, and the difference was statistically significant. Meta-analysis of four HLA-DR matching articles showed OR =0.69, 95% CI: (0.41, 1.17), significance test Z=1.39, P=0.17, and the difference was not statistically significant. DISCUSSION: In patients with infectious keratitis undergoing corneal transplantation, preoperative matching of HLA-A, HLA-B, and HLA-DR sites played an important role in corneal transplantation. Preoperative HLA matching is of clinical significance.

In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration.

Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.

FasL expression on human nucleus pulposus cells contributes to the immune privilege of intervertebral disc by interacting with immunocytes.

The mechanisms of immune privilege in human nucleus pulposus (NP) remain unclear. Accumulating evidence indicates that Fas ligand (FasL) might play an important role in the immune privilege of the disc. We aimed for addressing the role of FasL expression in human intervertebral disc degeneration (IDD) and immune privilege in terms of the interaction between NP cells and immunocytes via the FasL-Fas machinery. We collected NP specimens from 20 patients with IDD as degenerative group and 8 normal cadaveric donors as control. FasL expression was detected by qRT-PCR, western blotting and flow cytometry (FCM). We also collected macrophages and CD8(+) T cells from the peripheral blood of patients with IDD for co-cultures with NP cells. And macrophages and CD8(+) T cells were harvested for apoptosis analysis by FCM after 2 days of co-cultures. We found that FasL expression in mRNA, protein and cellular resolutions demonstrated a significant decrease in degenerative group compared with normal control (p<0.05). FCM analysis found that human NP cells with increased FasL expression resulted in significantly increased apoptosis ratio of macrophages and CD8(+) T cells. Our study demonstrated that FasL expression tends to decrease in degenerated discs and FasL plays an important role in human disc immune privilege, which might provide a novel target for the treatment strategies for IDD.

Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats.

PURPOSE: To explore the feasibility of bone marrow mesenchymal stem cells (MSCs) transdifferentiating into corneal epithelial cells in a limbal stem cell deficiency (LSCD) model in rats. METHODS: Rat MSCs were isolated and purified using a gradient isolation procedure. The cells were induced by rat corneal stromal cells (CSCs) in a transwell co-culture system. The induced MSCs were identified by immunofluorescence staining, flow cytometry, and scanning electron microscopy (SEM). A corneal LSCD model was produced in the right eyes of 48 rats by alkali injury. The eyes of 12 rats without any transplant served as controls (Group 1). Amniotic membranes (AM; Group 2), uninduced MSCs (Group 3), or MSCs induced by CSCs (Group 4), were transplanted onto the cornea of the model (n=12 each). The therapeutic effects of the four groups were evaluated by slit lamp observation, hematoxylin and eosin staining, immunohistochemistry staining, and confocal laser corneal microscopy. RESULTS: Cultivated MSCs were positive for CD29, CD44, and CD90, but negative for CD34, CD45, CD133, and CK12, with typical MSCs characteristics revealed by SEM. After co-culture with CSCs, the induced MSCs expressed positive staining for CK12 with corneal epithelial cell characteristics confirmed by SEM; the induced MSCs were unchanged on the amnion. Compared with the other three groups, the corneal opacity, fluorescence staining, and neovascularization grades were significantly decreased in the induced MSCs group, both on postoperative week four and ten. CONCLUSION: MSCs induced by CSCs can transdifferentiate into corneal epithelial cells in vitro. The induced MSCs on an amniotic membrane have remarkable effects on the treatment of corneal alkali burn and the reconstruction of the corneal surface of rats.

Focal adhesion kinase signaling pathway participates in the formation of choroidal neovascularization and regulates the proliferation and migration of choroidal microvascular endothelial cells by acting through HIF-1 and VEGF expression in RPE cells.

Choroidal neovascularization (CNV) is one of the most frequent causes of severe and progressive vision loss, while its pathogenesis is still poorly understood. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, plays a crucial role in linking signals initiated by both the extracellular matrix (ECM) and soluble signaling factors and controls essential cellular processes. Extensive evidence has shown that FAK is activated in angiogenic response. This study aims to investigate the effect of FAK on CNV formation. The Brown-Norway (BN) rats underwent laser rupture of Bruch's membrane to induce CNV and were then killed at 1, 3, 7, and 14 days following laser injury. Immunofluorescence and Western blot were processed to detect FAK protein. Retinal pigment epithelial (RPE) cells were cultured under hypoxia and RNA interference (RNAi) technique was used to knock down the FAK gene in RPE cells. Expression of hypoxia inducible factor-1 (HIF-1alpha) and vascular endothelial growth factor (VEGF) in RPE cells were investigated by RT-PCR and Western blot. Two kinds of coculture models were used to observe the effects of specific blockade of FAK in RPE cells on the proliferation and migration of choroidal microvascular endothelial cells (CECs), respectively. FAK was highly expressed in the rat RPE-choroid tissue after photocoagulation. In vitro experiment showed that FAK was involved in hypoxia signaling in cultured RPE cells. The absence of FAK effectively reduced the expression of hypoxia-induced HIF-1alpha and VEGF in RPE cells, resulting in the inhibition of proliferation and migration of CECs. Our results suggest that FAK pathway activation plays a role in the development of CNV, and regulates the proliferation and migration of CECs by acting through HIF-1 and then up-regulating the expression of the angiogenic factor VEGF in RPE cells. It is reasonable to propose that FAK siRNA will potentially provides a means to attenuate the strong stimuli for neovascularization in CNV-dependent disorders, which could present a therapeutically relevant strategy for the inhibition of CNV.