Update on autoimmune retinopathy: diagnosis and management.

Purpose Of Review: Autoimmune retinopathy (AIR) is a rare but vision-threatening disorder characterized by retinal damage through humoral or cellular immune mechanisms. The purpose of this review is to summarize our current understanding on imaging, antibody testing, and immunosuppressive therapies for AIR.

Recent Findings: AIR includes paraneoplastic forms - such as cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR) - as well as a nonparaneoplastic (np) variant (npAIR).

Calcitonin Gene-Related Peptide Ameliorates Experimental Dry Eye Disease.

Purpose: Calcitonin gene-related peptide (CGRP) level is reduced in the tears of patients with dry eye disease (DED). The current study aims to investigate the expression and therapeutic potential of CGRP as topical eye drops in treating experimental DED.

Methods: Human corneal epithelial cells (CECs) were cultured under hyperosmotic stress (HS) and the effects of CGRP on cell viability, proliferation, migration, and apoptosis were determined in vitro.

Topical Hepatocyte Growth Factor Accelerates Wound Healing and Inhibits Scarring in Experimental Corneal Injury.

Purpose: The aim of this study was to compare the rates of healing, scar formation, and regression of preexisting scars using topical murine hepatocyte growth factor (mHGF), recombinant human deleted HGF (dHGF), murine nerve growth factor (mNGF), and phosphate-buffered saline (PBS).

Methods: Mechanical corneal epithelial and stromal injury was induced in C57BL/6 mice. Five groups of mice were studied in each of phase I (wound healing and scar formation) and phase II (regression of preexisting scars).

Hepatocyte growth factor upregulates MMP1 and MMP10 expression and resolves corneal fibrosis.

Different therapeutic modalities, including steroids, have been used to treat corneal scarring. However, the ability of steroids to reduce corneal scarring is limited and associated with numerous side effects. Our previous studies have demonstrated that topical hepatocyte growth factor (HGF) after corneal injury suppresses the development of stromal scars.

Effector T Cells Promote Fibrosis in Corneal Transplantation Failure.

Purpose: To evaluate whether fibrosis contributes to corneal transplant failure and to determine whether effector CD4+ T cells, the key immune cells in corneal transplant rejection, play a direct role in fibrosis formation.

Methods: Allogeneic corneal transplantation was performed in mice. Graft opacity was evaluated by slit-lamp biomicroscopy, and fibrosis was assessed by in vivo confocal microscopy.

Topical application of calcitonin gene-related peptide as a regenerative, antifibrotic, and immunomodulatory therapy for corneal injury.

Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide abundantly expressed by corneal nerves. Using a murine model of corneal mechanical injury, we found CGRP levels in the cornea to be significantly reduced after injury. Topical application of CGRP as an eye drop three times daily accelerates corneal epithelial wound closure, reduces corneal opacification, and prevents corneal edema after injury in vivo.

Increased activity of lacrimal gland mast cells are associated with corneal epitheliopathy in aged mice.

The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy.

IL-36γ Augments Ocular Angiogenesis by Promoting the Vascular Endothelial Growth Factor-Vascular Endothelial Growth Factor Receptor Axis.

Prevention of inflammatory angiogenesis is critical for suppressing chronic inflammation and inhibiting inflammatory tissue damage. Angiogenesis is particularly detrimental to the cornea because pathologic growth of new blood vessels can lead to marked vision impairment and even loss of vision. The expression of proinflammatory cytokines by injured tissues exacerbates the inflammatory cascade, including angiogenesis.

Non-immune and immune functions of interleukin-36γ suppress epithelial repair at the ocular surface.

Regulation of innate inflammation is critical for maintaining tissue homeostasis and barrier function, especially in those interfacing the external environments such as the skin and cornea. Expression of pro-inflammatory cytokines by injured tissues has been shown to exacerbate the inflammatory cascade, causing tissue damage. Interleukin 36, a subfamily of the IL-1 superfamily, consists of three pro-inflammatory agonists-IL36α, IL36β, and IL36γ and an IL36 receptor antagonist (IL36Ra).

Ocular surface mast cells promote inflammatory lymphangiogenesis.

Mast cells, sentinel immune cells, are most abundantly expressed in vascularized tissues that interface the external environment, such as the skin and ocular surface. Our previous reports have shown mast cells reside closely with vascular endothelial cells and mediate the pathogenic angiogenic response. However, the contribution of mast cells and their underlying mechanisms on lymphangiogenesis have not been fully deciphered.

Suppression of lipopolysaccharide-induced corneal opacity by hepatocyte growth factor.

Keratitis induced by bacterial toxins, including lipopolysaccharide (LPS), is a major cause of corneal opacity and vision loss. Our previous study demonstrates hepatocyte growth factor (HGF) promotes epithelial wound healing following mechanical corneal injury. Here, we investigated whether HGF has the capacity to suppress infectious inflammatory corneal opacity using a new model of LPS-induced keratitis.

Spatial Distribution of Mast Cells Regulates Asymmetrical Angiogenesis at the Ocular Surface.

Mast cells, historically known for their function as effector cells in the induction of allergic diseases, reside in all vascularized tissues of the body, particularly, in proximity to blood and lymphatic vessels. Despite being neighboring sentinel cells to blood vessels, whether the spatial distribution of mast cells regulates the degree of angiogenesis remains to be investigated. Herein, an asymmetrical distribution of mast cells was shown at the murine ocular surface, with the higher number of mast cells distributed along the nasal limbus of the cornea compared with the temporal side.

Activation of ocular surface mast cells promotes corneal neovascularization.

Purpose: Mast cells, historically known for their effector function in the induction of allergic diseases, reside in all vascularized tissues of the body in particular proximity to blood and lymphatic vessels. As neighboring sentinel cells to blood vessels, mast cells have been associated with angiogenesis. Here we assess the direct contribution of mast cells to neovascularization at the ocular surface.

Recent advances in the management of non-infectious posterior uveitis.

Purpose: To review the current regimens and novel therapeutic modalities in various stages of research and development for the management of non-infectious posterior uveitis (NIPU).

Methods: We performed a thorough review of current literature using PubMed, Google Scholar and Clinicaltrials.gov to identify the published literature about the available therapeutics and novel drugs/therapies in different stages of clinical trials.

Mesenchymal Stromal Cells Modulate Corneal Alloimmunity via Secretion of Hepatocyte Growth Factor.

Mesenchymal stromal cells (MSCs) are multipotent stem cells that participate in tissue repair and possess considerable immunomodulatory potential. MSCs have been shown to promote allograft survival, yet the mechanisms behind this phenomenon have not been fully defined. Here, we investigate the capacity of MSCs to suppress the allogeneic immune response by secreting the pleiotropic molecule hepatocyte growth factor (HGF).