A Novel Murine Model of Radiation Keratopathy

Harris, Deshea L; Yamaguchi, Takefumi; Hamrah, Pedram

doi:10.1167/iovs.18-24567

Cited by 10 publications

(7 citation statements)

References 59 publications

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“…Corneal hydration has been extensively studied from basic principles to clinical practice, including transport mechanisms for water in the cornea [16][17][18][19], factors affecting corneal hydration [20][21][22] and influences on corneal surgeries [23][24][25][26][27]. However, corneal dehydration, an important aspect of corneal hydrodynamics, lacks in-depth research.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo quantitative analysis of human corneal stroma dehydration by near‐infrared absorption spectroscopy

Sun

et al. 2019

Journal of Biophotonics

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Corneal water content and hydrodynamics are critical indicators of eye health. In this work, a convenient method based on near‐infrared absorption spectroscopy (NIRA) was presented to measure the relative water content of the corneal stroma ex vivo, which paves the way to measure corneal water content in vivo. The relative water content of fresh corneal stroma during dehydration under natural conditions (temperature, 25.8 ± 0.3°C; humidity, 7.2% ± 0.9%) was monitored in real time, and the characteristic time τ when the relative water content dropped to 90% of the fresh corneal stroma was 140.1 ± 30.6 s. Furthermore, the change in the relative water content over time was found to be linear with a dehydration rate of 0.071% per second, consistent with indirect optical coherence pachymetry but with superior reproducibility and precision. Provided that the NIRA spectrometer is changed to a reflection structure from the current transmission configuration, the NIRA method proposed in this work has great potential for in vivo measurement with the advantages of non‐contact, high precision and low cost.

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Section: Introductionmentioning

confidence: 99%

Ex vivo quantitative analysis of human corneal stroma dehydration by near‐infrared absorption spectroscopy

Sun

et al. 2019

Journal of Biophotonics

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“…3 B), possibly due to aging or irradiation, as radiation stress has been previously shown to cause corneal keratopathy. 29 , 30 …”

Section: Resultsmentioning

confidence: 99%

Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis

Shamloo

Weng

Ross

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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Purpose The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin–angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)–associated conjunctival fibrosis. Methods A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. Eyes were harvested at 4 and 8 weeks after the transplant for alpha-smooth muscle actin (α-SMA), angiotensinogen, and angiotensin-converting enzyme (ACE) immunostaining. Conjunctiva was harvested for gene expression quantification of α-SMA, angiotensinogen, and ACE. Results More than 80% of the spleen cells in the recipient mice were chromosome Y positive, thus conforming successful engraftment. A significant decrease in tear secretion and a marked increase in corneal keratopathy score after allogeneic transplantation indicated the onset of ocular GVHD in these mice. A significant increase in α-SMA gene expression and the presence of a large number of α-SMA–positive cells was noted in the bulbar orbital conjunctiva of mice after allogeneic transplantation. Allogenic transplantation also caused a significant increase in the gene expression and protein expression of angiotensinogen and ACE in the subconjunctival eyelid area. Conclusions Results of the present study demonstrate that GVHD-associated conjunctival fibrosis is accompanied by myofibroblast formation and activation of the local conjunctival RAS.

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“…This was reflected by the good final visual outcome observed in 3 patients (Patients 5–7). An in vitro murine model of radiation keratopathy recently reported by Harris et al [23] demonstrated significant loss of corneal nerves with the influx and activation of immune cells within months of sublethal radiation. Unfortunately, no in vivo confocal microscopy facility was available in our unit to visualize the extent of damage to the corneal nerve.…”

Section: Discussionmentioning

confidence: 99%

Clinical Spectrum and Outcomes of Ocular and Periocular Complications following External-Beam Radiotherapy for Inoperable Malignant Maxillary Sinus Tumors

Ting

Rana-Rahman

et al. 2020

Ocul Oncol Pathol

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Purpose: To highlight the clinical spectrum, management, and outcomes of ocular/periocular complications following high-dose external-beam radiotherapy (EBRT) for inoperable malignant maxillary sinus-involving tumors (MMST). Methods: A retrospective, interventional case series. All patients who were diagnosed with inoperable MMST (with orbital involvement) and treated with high-dose fractionated EBRT (65 Gy in 30 fractions) at James Cook University Hospital, UK, were included. Results: Seven patients with advanced MMST (T4aN0M0–T4bN2cM0) were included and were followed up for 23.8 ± 10.2 months. Severe lid margin disease, dry eye, and neurotrophic keratopathy were universally observed. Other complications included cicatricial conjunctivitis (71%), corneal perforation (57%), limbal stem cell deficiency (LSCD; 43%), glaucoma (29%), and superimposed candida keratitis (14%). Amniotic membrane transplant (AMT; 71%), tarsorrhaphy (43%), tectonic keratoplasty (29%), and evisceration (14%) were warranted. Intact corneal epithelium was observed in all patients and good corrected-distance visual acuity (≥20/60) was observed in 3 (43%) patients at final follow-up. Conclusion: High-dose EBRT for inoperable MMST can lead to a wide array of severe ocular/periocular complications. AMT serves as a potentially useful treatment modality to restore the ocular surface integrity after severe radiation keratopathy. We advocate active monitoring for any evolving ophthalmic complications during and after EBRT to enable timely intervention.

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A Novel Murine Model of Radiation Keratopathy

Cited by 10 publications

References 59 publications

Ex vivo quantitative analysis of human corneal stroma dehydration by near‐infrared absorption spectroscopy

Ex vivo quantitative analysis of human corneal stroma dehydration by near‐infrared absorption spectroscopy

Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease–Associated Conjunctival Fibrosis

Clinical Spectrum and Outcomes of Ocular and Periocular Complications following External-Beam Radiotherapy for Inoperable Malignant Maxillary Sinus Tumors

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