Comprehensive Modeling of Corneal Alkali Injury in the Rat Eye

Choi, Hosoon; Phillips, Casie; Oh, Joo Youn; Stock, Eileen M.; Kim, Yon Su; Won, Jae Kyung; Fulcher, Samuel

doi:10.1080/02713683.2017.1317817

Cited by 47 publications

(52 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alkali injury of the cornea is one of the most devastating ophthalmic conditions [ 12 ] and can cause epithelial defects, acute inflammation, neovascularization, and decreased transparency of the cornea, resulting in blindness. The purpose of this study was to demonstrate the effect of a PPARβ/δ agonist using a rat corneal alkali burn model, which is widely used to study the mechanisms of treatments, acute inflammation, and neovascularization in the injured cornea [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor Beta/Delta Agonist Suppresses Inflammation and Promotes Neovascularization

Tobita

Arima

Nakano

et al. 2020

IJMS

View full text Add to dashboard Cite

The effects of peroxisome proliferator-activated receptor (PPAR)β/δ ophthalmic solution were investigated in a rat corneal alkali burn model. After alkali injury, GW501516 (PPARβ/δ agonist) or vehicle ophthalmic solution was topically instilled onto the rat’s cornea twice a day until day 7. Pathological findings were evaluated, and real-time reverse transcription polymerase chain reaction was performed. GW501516 strongly suppressed infiltration of neutrophils and pan-macrophages, and reduced the mRNA expression of interleukin-6, interleukin-1β, tumor necrosis factor alpha, and nuclear factor-kappa B. On the other hand, GW501516 promoted infiltration of M2 macrophages, infiltration of vascular endothelial cells associated with neovascularization in the wounded area, and expression of vascular endothelial growth factor A mRNA. However, 7-day administration of GW501516 did not promote neovascularization in uninjured normal corneas. Thus, the PPARβ/δ ligand suppressed inflammation and promoted neovascularization in the corneal wound healing process. These results will help to elucidate the role of PPARβ/δ in the field of ophthalmology.

show abstract

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor Beta/Delta Agonist Suppresses Inflammation and Promotes Neovascularization

Tobita

Arima

Nakano

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…For corneal epithelial defect quantification, 3% lissamine green vital dye (Lissamine TM Green B dye, Sigma-Aldrich) was applied to the corneal surface, and the stained epithelial defect was graded based on the Oxford scale 32 . Corneal opacity was graded based on the previously-reported scoring system 33 . The grading was carried out by a corneal specialist (K.W.K) in a blind manner.…”

Section: Clinical Examination Of Corneal Epithelial Defects and Strommentioning

confidence: 99%

FUT1 deficiency elicits immune dysregulation and corneal opacity in steady state and under stress

Kim

Ryu

et al. 2020

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Fucosylation is a biological process that plays a critical role in multiple cellular functions from cell adhesion to immune regulation. Fucosyltransferases (FUTs) mediate fucosylation, and dysregulation of genes encoding FUTs is associated with various diseases. FUT1 and its fucosylated products are expressed in the ocular surface and ocular adnexa; however, the role of FUT1 in the ocular surface health and disease is yet unclear. Here, we investigated the effects of FUT1 on the ocular surface in steady-state conditions with age and under desiccating stress using a Fut1 knockout (KO) mouse model. We found that corneal epithelial defects and stromal opacity developed in Fut1 KO mice. Also, inflammatory responses in the ocular surface and Th1 cell activation in ocular draining lymph nodes (DLNs) were upregulated. Desiccating stress further aggravated Th1 cell-mediated immune responses in DLNs, lacrimal gland, and ocular surface in Fut1 KO mice, leading to severe corneal epithelial disruption and opacity. Mixed lymphocyte reaction assays revealed that the activity of splenocytes to stimulate CD4 T-cell proliferation was increased in Fut1 KO mice. Together, these data demonstrate that FUT1 deficiency induces immune dysregulation in the ocular surface and corneal opacity in steady state and under desiccating stress.

show abstract

“…Recovery, if possible, occurs over weeks to months. This protracted course is also encountered in rodents 41 . However, after chemical corneal injury, rapid reepithelialization is necessary to restore the protective barrier of tight junctions and limit recruitment of inflammatory cells, thereby reducing the risk of infection, scarring, persistent corneal defects, and other sight-threatening sequelae.…”

Section: Discussionmentioning

confidence: 56%

Neprilysin inhibition promotes corneal wound healing

Genova

Meyer

Anderson

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Neprilysin (NEP), an ectoenzyme that modulates inflammation by degrading neuropeptides, was recently identified in the human corneal epithelium. The cornea expresses many NEP substrates, but the function of NEP in homeostatic maintenance and wound healing of the cornea is unknown. We therefore investigated the role of this enzyme under naive and injured conditions using NEP-deficient (NEP−/−) and wild type (WT) control mice. In vivo ocular surface imaging and histological analysis of corneal tissue showed no differences in limbal vasculature or corneal anatomy between naive NEP−/− and WT mice. Histological examination revealed increased corneal innervation in NEP−/− mice. In an alkali burn model of corneal injury, corneal wound healing was significantly accelerated in NEP−/− mice compared to WT controls 3 days after injury. Daily intraperitoneal administration of the NEP inhibitor thiorphan also accelerated corneal wound healing after alkali injury in WT mice. Collectively, our data identify a previously unknown role of NEP in the cornea, in which pharmacologic inhibition of its activity may provide a novel therapeutic option for patients with corneal injury.

show abstract

Comprehensive Modeling of Corneal Alkali Injury in the Rat Eye

Abstract: This study highlights the molecular, clinical, and histopathological changes throughout the progression of alkali injury in the rat cornea. These profiles will assist in the development of new strategies and therapies for ocular alkali injury.

Cited by 47 publications

References 48 publications

Peroxisome Proliferator-Activated Receptor Beta/Delta Agonist Suppresses Inflammation and Promotes Neovascularization

Peroxisome Proliferator-Activated Receptor Beta/Delta Agonist Suppresses Inflammation and Promotes Neovascularization

FUT1 deficiency elicits immune dysregulation and corneal opacity in steady state and under stress

Neprilysin inhibition promotes corneal wound healing

Contact Info

Product

Resources

About