NGF modulates trkANGFR/p75NTR in αsMA-expressing conjunctival fibroblasts from human ocular cicatricial pemphigoid (OCP)

OBJECTIVE: In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. MATERIALS AND METHODS: Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFβ1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. RESULTS: OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both αSMA/p75NTR expression and TGFβ1/IL4 release. These effects were not observed in advanced OCP-FBs. CONCLUSIONS: Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target

How latanoprost changed glaucoma management

Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes

Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva

Purpose: To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients.Methods: Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alpha SMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels.Results: Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed aSMA and increased types I and IV collagens. VKC-FBs, and in particular all aSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change aSMA expression, while aSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein.Conclusions: The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC

MicroShunt versus trabeculectomy for surgical management of glaucoma: a retrospective analysis

This case-control study aims to compare the efficacy, safety, and postoperative burden of MicroShunt versus trabeculectomy. The first consecutive cohort of MicroShunt procedures (n = 101) was matched to recent historical trabeculectomy procedures (n = 101) at two London hospital trusts. Primary endpoints included changes in intraocular pressure (IOP) and glaucoma medications. Secondary outcome measures included changes in retinal nerve fibre layer (RNFL) thickness, rates of complications, further theatre interventions, and the number of postoperative visits. From the baseline to Month-18, the median [interquartile range] IOP decreased from 22 [17–29] mmHg (on 4 [3–4] medications) to 15 [10–17] mmHg (on 0 [0–2] medications) and from 20 [16–28] mmHg (on 4 [3–4] medications) to 11 [10–13] mmHg (on 0 [0–0] medications) in the MicroShunt and trabeculectomy groups, respectively. IOP from Month-3 was significantly higher in the MicroShunt group (p = 0.006), with an increased number of medications from Month-12 (p = 0.024). There were greater RNFL thicknesses from Month-6 in the MicroShunt group (p = 0.005). The rates of complications were similar (p = 0.060) but with fewer interventions (p = 0.031) and postoperative visits (p = 0.001) in the MicroShunt group. Therefore, MicroShunt has inferior efficacy to trabeculectomy in lowering IOP and medications but provides a better safety profile and postoperative burden and may delay RNFL loss

Real-Time Imaging of Retinal Cell Apoptosis by Confocal Scanning Laser Ophthalmoscopy and Its Role in Glaucoma

Glaucoma is one of the leading causes of irreversible blindness in the world. It is characterized by the progressive loss of retinal ganglion cells (RGCs), mainly through the process of apoptosis. Glaucoma patients often come to clinical attention when irreversible loss of visual function has been already established; therefore, early recognition of RGC apoptosis is inordinately important in disease prevention. The novel technology called Detection of Apoptosing Retinal Cells (DARC) allows real-time in vivo quantification of apoptosing cells through the use of a fluorescent biomarker and a confocal scanning ophthalmoscope. A recent Phase I clinical trial has evaluated the safety of DARC and its ability to detect retinal apoptosis in glaucoma patients and healthy volunteers. Results suggest that DARC may have potential in the early detection of glaucoma, which could help alleviate the medical, social, and economic burden associated with this blinding condition

Oculo-visual abnormalities in Parkinson's disease: possible value as biomarkers.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and the second leading cause of dementia worldwide. With an aging population, the prevalence of the disease has dramatically increased. Clinical management has advanced through recent developments in dopaminergic imaging and genetic risk profiling. However, early and accurate diagnosis of the disorder remains a challenge, largely because of the lack of noninvasive and inexpensive reliable diagnostic tests. Besides the well-studied cerebral neurodegeneration that underlies the cardinal symptoms of PD (ie, bradykinesia, tremor, rigidity, and postural instability), ocular changes have also been described in PD, including visual dysfunction, pupil abnormality, lens opacity, and retinal neuronal loss and dysfunction. These ocular pathological processes are related to α-synuclein deposition, and dopamine deficiency in the retina-mirroring the defining pathological features of PD in the brain. Together, these observations support the notion that the eye can serve as a window to the brain, providing clinicians with noninvasive methods to visualize disease. This review focuses on recent advances in the characterization of ocular changes in PD and their promising use as biomarkers in the eye, which can be potentially used for aiding in early diagnosis, tracking disease progression, and valuating novel therapeutic strategies. © 2018 International Parkinson and Movement Disorder Society.status: publishe

Nerve growth factor modulates toll-like receptor (TLR) 4 and 9 expression in cultured primary VKC conjunctival epithelial cells

To investigate if nerve growth factor (NGF) might modulate toll-like receptor (TLR) 4 and 9 expression in primary cultures of vernal keratoconjunctivitis (VKC)-derived conjunctival epithelial cells (VKC-ECs)

Natural killer cells in vernal keratoconjunctivitis

Recent studies suggest that natural killer (NK) cells exert effector/regulatory properties on both innate and adaptive responses via release of different cytokines. While some information indicates NK cells in allergic asthma and atopic dermatitis, no data are available for allergic conjunctivitis. The aim of this study was to evaluate NK in the blood and the conjunctiva of patients with vernal keratoconjunctivitis (VKC)

Histological characterization of OCP conjunctivas.

<p>Representative confocal (A-B) and light microscopy (C-H) images, including Giemsa (CD), HE (EF) and PAS (GH) stainings, from dewaxed conjunctival sections. A-B. Linear fluorescent-coupled IgGAM reactivity in the Basement Membrane Zone of <i>early</i> (white arrows; A) and <i>advanced</i> (B; the white asterisk indicates the stromal immunoreactivity) OCP sections. Fluorescent linear immunoreactivity is absent in normal sections. Depletion of goblet cells (pointed by black arrowheads) in <i>early</i> (C,E,G) with respect to the complete absence in <i>advanced</i> OCP (D,F,H); the presence of a squamous metaplasia (↔) particularly in <i>advanced</i> OCP (D,F); vessel ectasia (*) more prominent in <i>early</i> (E) than <i>advanced</i> (F); edema with mild infiltrates (arrows) in <i>early</i> (C) and to a less extend in <i>advanced</i> (D) OCP, particularly plasmacells and some granulocytes; and finally superficial homogenization of connective tissue (§), particularly evident in <i>advanced</i> OCP (D,F). Magnifications: x400.</p