Cellular response to inflammation at the limbus

Smolin, Gilbert

doi:10.1038/eye.1989.24

Cited by 13 publications

(4 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD19-expressing B cells and CD33-expressing mononuclear cells are not present within the healthy cornea, but may be delivered from the limbus and/or conjunctiva to the corneal epithelium through centripetal migration. [98][99][100] Others such as CD70 and CD138 may be present in corneal dendritic cells or corneal epithelial cells, respectively, but not in abundance. 67,98,101 Furthermore, ephrin type A is only found at low levels and in many tissues, and DS6 is only reported on the surfaces of solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

Eaton¹,

Miller

Mannis

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

206

193

View full text Add to dashboard Cite

This article reviews ocular adverse events (AEs) reported in association with administration of antibody-drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials.

show abstract

Section: Discussionmentioning

confidence: 99%

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

Eaton¹,

Miller

Mannis

et al. 2015

Journal of Ocular Pharmacology and Therapeutics

206

193

View full text Add to dashboard Cite

show abstract

“…There exist a host of mediators that have been implicated in the development and progression of corneal inflammation (2,3). The source of these mediators may be the injured tissue or infiltrating inflammatory cells.…”

mentioning

confidence: 99%

Regulation of Cyclooxygenase-2 by Hypoxia and Peroxisome Proliferators in the Corneal Epithelium

Bonazzi¹,

Mastyugin

Mieyal

et al. 2000

Journal of Biological Chemistry

116

View full text Add to dashboard Cite

Hypoxic injury provokes inflammation of many tissues including the ocular surface. In rabbit corneal epithelial cells, both peroxisome proliferator-activated receptor (PPAR)-inducible cytochrome P450 4B1 and cyclooxygenase-2 (COX-2) mRNAs were increased by hypoxia. PPAR ␣ and ␤ but not ␥ mRNAs were detected in these cells. The PPAR activator, WY-14,643 increased COX-2 expression. Similarly, non-steroidal anti-inflammatory drugs with the ability to activate PPARs induced COX-2 independently of prostaglandin synthesis inhibition. COX-2 protein overexpression by hypoxia and PPAR activation was not associated with a parallel increase in prostaglandin E 2 accumulation. However, the enzyme regained full catalytic activity when: 1) hypoxic cells were re-exposed to normoxic conditions in the presence of heme and arachidonic acid, and 2) WY-14,643-treated cells were depleted of intracellular GSH. Consistent with previous observations showing that the corneal production of cytochrome P450-derived inflammatory eicosanoids is elevated by hypoxia and inflammation, the current data suggest that hypoxic injury is a model of inflammation in which molecules other than COX-derived arachidonic acid metabolites play a major proinflammatory role. This study also suggests that increased cellular GSH may be the mechanism responsible for the characteristic dissociation of PPAR-induced COX-2 expression and activity. Moreover, we provide new insights into the commonly observed lack of efficacy of classical non-steroidal anti-inflammatory drugs in the treatment of hypoxia-related ocular surface inflammation.

show abstract

“…The corneal wound healing process constitutes a resurfacing of corneal epithelial cells, a reorganization of the basement membrane, and the regeneration of ECM components [ 69 ]. The cellular immune response in the limbal precorneal region plays an essential role in these processes, maintaining the corneal epithelium and contributing to epithelial wound healing [ 70 , 71 ]. Corneal wound healing is discussed in a separate section below.…”

Section: Wound Healingmentioning

confidence: 99%

Autophagy in Extracellular Matrix and Wound Healing Modulation in the Cornea

Kempuraj

Mohan

2022

Biomedicines

View full text Add to dashboard Cite

Autophagy is a robust cellular mechanism for disposing of harmful molecules or recycling them to cells, which also regulates physiopathological processes in cornea. Dysregulated autophagy causes inefficient clearance of unwanted proteins and cellular debris, mitochondrial disorganization, defective inflammation, organ dysfunctions, cell death, and diseases. The cornea accounts for two-thirds of the refraction of light that occurs in the eyes, but is prone to trauma/injury and infection. The extracellular matrix (ECM) is a noncellular dynamic macromolecular network in corneal tissues comprised of collagens, proteoglycans, elastin, fibronectin, laminins, hyaluronan, and glycoproteins. The ECM undergoes remodeling by matrix-degrading enzymes and maintains corneal transparency. Autophagy plays an important role in the ECM and wound healing maintenance. Delayed/dysregulated autophagy impacts the ECM and wound healing, and can lead to corneal dysfunction. Stromal wound healing involves responses from the corneal epithelium, basement membrane, keratocytes, the ECM, and many cytokines and chemokines, including transforming growth factor beta-1 and platelet-derived growth factor. Mild corneal injuries self-repair, but greater injuries lead to corneal haze/scars/fibrosis and vision loss due to disruptions in the ECM, autophagy, and normal wound healing processes. Presently, the precise role of autophagy and ECM remodeling in corneal wound healing is elusive. This review discusses recent trends in autophagy and ECM modulation in the context of corneal wound healing and homeostasis.

show abstract

Cellular response to inflammation at the limbus

Cited by 13 publications

References 11 publications

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

Regulation of Cyclooxygenase-2 by Hypoxia and Peroxisome Proliferators in the Corneal Epithelium

Autophagy in Extracellular Matrix and Wound Healing Modulation in the Cornea

Contact Info

Product

Resources

About