Animal models of high-risk corneal transplantation: a comprehensive review

Over the past century, corneal transplantation has become the most commonly performed allogeneic solid tissue transplantation. Although more than 80% of the corneal transplantations have favorable outcomes, immune-mediated rejection continues to be the major cause of failure in well over 50% of graft recipients that have inflamed and vascularized host beds. Over the past two decades, the progress in our understanding of the immunological pathways that mediate graft rejection has aided in the development of novel therapeutic strategies. In order to successfully test the efficacy of these interventions, it is essential to model the immunological processes occurring as a consequence of corneal transplantation. Herein, we have comprehensively reviewed the established animal models used for replicating the immunopathological processes causing graft rejection in high-risk corneal transplantation settings. We have also discussed the practical and technical differences, as well as biological and immunological variations in different animal models

Restoration of regulatory T-cell function in dry eye disease by antagonizing substance P/neurokinin-1 receptor

Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity

Outcomes of primary rhegmatogenous retinal detachment repair with extensive scleral-depressed vitreous removal and dynamic examination.

There are multiple surgical approaches to the repair of rhegmatogenous retinal detachment (RRD). Here, we evaluated the outcomes of small-gauge pars plana vitrectomy (PPV), alone or in combination with scleral buckle (SB-PPV), for RRD repair using a standardized technique by 3 vitreoretinal surgeons: "extensive" removal of the vitreous with scleral depression and dynamic examination of the peripheral retina. One hundred eighty seven eyes of 180 consecutive patients treated for primary RRD by three vitreoretinal surgeons at a tertiary academic medical center from September 2015 to March 2018 were analyzed. Most RRDs occurred in males (134 [71.3%] eyes), affected the left eye (102 [54.3%]), and were phakic (119 [63.3%]). PPV alone was performed in 159 eyes (84.6%), with a combined SB-PPV used in the remaining 29 eyes (15.4%); focal endolaser was used in all (100%) cases. The single surgery anatomic success rate was 186 eyes (99.5%) at 3 months, and 187 (100%) at last follow up. Overall best-corrected visual acuity (BCVA) had significantly improved at 3 months ([Snellen 20/47] P<0.00005) and last follow up ([Snellen 20/31] P<0.00005), as compared to day of presentation ([Snellen 20/234]). Our findings suggest that "extensive" removal of the vitreous and dynamic peripheral examination with scleral depression may lead to high single surgery success in primary uncomplicated RRD repair

Neuropeptide substance P and the immune response

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response