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Hypoxia adaptation in the cornea:Current animal models and underlying mechanisms

Animal Models and Experimental Medicine 2021年第4期4卷 300-310页

作者： Kunpeng Pang anton lennikov Menglu Yang Harvard Medical School Department of Ophthalmology Schepens Eye Research InstituteMassachusetts Eye and EarBostonMassachusettsUSA Department of Ophthalmology Qilu Hospital of Shandong UniversityQingdaoChina

The cornea is an avascular,transparent tissue that is essential for visual *** disturbance to the corneal transparency will result in a severe vision *** to the avascular nature,the cornea acquires most of the oxygen supply directly or indirectly from the *** tissue hypoxia has been noticed to influence the structure and function of the cornea for *** etiology of hypoxia of the cornea is distinct from the rest of the body,mainly due to the separation of cornea from the atmosphere,such as prolonged contact lens wearing or closed *** hypoxia can also be found in corneal inflammation and injury when a higher oxygen requirement exceeds the oxygen *** hypoxic state during lung diseases or high altitude also leads to corneal hypoxia when a second oxygen consumption route from aqueous humor gets *** affects the cornea in multiple aspects,including disturbance of the epithelium barrier function,corneal edema due to endothelial dysfunction and metabolism changes in the stroma,and thinning of corneal *** has also evolved mechanisms to adapt to the hypoxic state initiated by the activation of hypoxia inducible factor(HIF).The aim of this review is to introduce the pathology of cornea under hypoxia and the mechanism of hypoxia adaptation,to discuss the current animal models used in this field,and future research directions.

关键词： animal model contact lens wear cornea hypoxia hypoxia adaptation hypoxia inducible factor(HIF)

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Modified streptozotocin-induced diabetic model in rodents

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Animal Models and Experimental Medicine 2024年第5期7卷 777-780页

作者： anton lennikov Farris ElZaridi Menglu Yang Department of Ophthalmology Schepens Eye Research InstituteMass Eye and EarHarvard Medical SchoolBostonMassachusettsUSA

Streptozotocin(STZ)-induced type I diabetes mellitus(DM)models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglyce-mia akin to human type I ***,these models often suffer from poor induction rates and low survival post-STZ induction,especially in long-term experi-ments,necessitating insulin supplementation,which introduces additional variables to *** address this,we present a novel modification to the STZ-induced DM model in C57BL/6J mice to improve survival rates without insulin *** method involves non-fasting,low-dose STZ injections dissolved in pH-neutral phosphate buffer saline instead of acidic sodium citrate buffer,administered over 5 *** observed hyperglycemia induction in 94.28%of mice within a week post-injection,with stable high blood glucose levels,stable body weight,and minimal mortality up to 21 ***,omitting 10%sucrose in water and fasting did not affect hyperglycemia *** findings suggest that the modified protocol not only decreases the experimental effort of the researchers,but reduces animal stress and mortality,thus enhancing experimental outcomes and animal *** opti-mizing the STZ-induced DM model in C57BL/6J mice,our study provides a valuable resource for researchers aiming to study diabetes and its complications while mini-mizing experimental variability and animal usage.

关键词： hyperglycemia non- fasting streptozotocin Type 1 diabetes mellitus

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Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

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Neural Regeneration Research 2024年第11期19卷 2543-2552页

作者： Sam Enayati Karen Chang anton lennikov Menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen Schepens Eye Research Institute of Massachusetts Eye and Ear Department of OphthalmologyHarvard Medical SchoolBostonMAUSA Institute of clinical medicine Faculty of MedicineUniversity of OsloOsloNorway Department of Medical Biochemistry Oslo University HospitalUniversity of OsloOsloNorway Department of Ophthalmology Drammen HospitalVestre Viken Hospital TrustDrammenNorway Department of Histology and Embryology School of MedicineMarmara UniversityIstanbulTurkiye

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor *** research supports the beneficial effect of electrical stimulation on photoreceptor *** study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal ***,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem *** this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp *** investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with *** retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in *** density was evaluated by rhodopsin *** vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp *** function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),*** was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse *** recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest *** of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human *** tem

关键词： bipolar cells electrical stimulation neuroprotection photoreceptor degeneration retina retinal explants retinitis pigmentosa transcorneal electrical stimulation waveform

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