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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

Low-cost real-time VLSI system for high-accuracy optical flow estimation using biological motion features and random forests

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Science China(Information Sciences) 2023年第5期66卷 301-302页

作者： Cong SHI Junxian HE Shrinivas PUNDLIK Xichuan ZHOU Nanjian WU Gang LUO School of Microelectronics and Communication Engineering Chongqing University schepens eye research institute Massachusetts Eye and Ear Harvard Medical School State Key Laboratory for Superlattices and Microstructures Institute of Semiconductors Chinese Academy of Sciences

This study proposes a low-cost, real-time, very large-scale integration (VLSI) architecture for optical flow *** architecture adopts parallel spatiotemporal filters to extract bio-inspired motion features at each pixel location and uses hardware random forests to infer the motion *** system achieves higher estimation accuracy at low computational hardware costs under real-time constraint than previous biological motion estimation systems.

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Cryopreserved limbal lamellar keratoplasty for peripheral corneal and limbal reconstruction

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International Journal of Ophthalmology(English edition) 2018年第4期11卷 699-702页

作者： Hua-Tao Xie Jing Li Yang Liu Dong-Ling Jiang Rui-Fen Shen Ming-Chang Zhang Department of Ophthalmology Union Hospital Tongji Medical College Huazhong University of Science and Technology schepens eye research institute Massachusetts Eye and Ear Harvard Medical School

This study aimed to evaluate the outcomes and described the recovery process of cryopreserved limbal lamellar keratoplasty（CLLK） for peripheral corneal and limbal diseases. Thirteen eyes of 12 patients with a mean age of 41±23.9 y were included. The average follow-up was 12.1±5.6 mo. Stable ocular surface was achieved in all eyes at last follow-up. Epithelialization originated from both recipient and graft in 9 eyes. We conclude that CLLK compensates for the shortage of donor corneas and cryopreserved limbal grafts provide epithelialization sources in ocular surface reconstruction.

关键词： cryopreserve epithelialization lamellar keratoplasty limbus neovascularization ocular surface peripheral corneal and limbal diseases stem cells

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

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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)

Non-invasive electrical stimulation as a potential treatment for retinal degenerative diseases

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Neural Regeneration research 2021年第8期16卷 1558-1559页

作者： Karen Chang Sam Enayati Kin-Sang Cho Tor P.Utheim Dong Feng Chen schepens eye research institute of massachusetts eye and ear Department of OphthalmologyHarvard Medical SchoolBostonMAUSA Department of Medical Biochemistry Oslo University HospitalOsloNorway Department of Ophthalmology Drammen HospitalNorway

More than 38.5 million people are estimated to be affected by blindness worldwide in 2020(Flaxman et al., 2017). Among the diseases that cause visual impairment, refractive errors are typically corrected with glasses and cataract with surgery. The leading causes of irreversible blindness nowadays are usually degenerative diseases related to the retina and its extending optic nerves.

关键词： glasses treatment typically

LIM kinases in synaptic plasticity and their potential as therapeutic targets

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Neural Regeneration research 2020年第8期15卷 1471-1472页

作者： Éva Halász Ellen Townes-Anderson Weiwei Wang Department of Pharmacology Physiology and NeuroscienceGraduate School of Biomedical SciencesRutgersThe State University of New JerseyNewarkNJUSA Grousbeck Gene Therapy Center Schepens Eye Research Institute and Massachusetts Eye and EarHarvard Medical SchoolBostonMAUSA

LIM domain kinases(LIMKs),which modulate cytoskeletal dynamics,are found throughout the central nervous *** synaptic junctions between neurons show structural alteration or plasticity during neurodevelopment,learning and memory formation,or after injury and disease;in some cases completely new connections form,while others are *** remodeling is under the control of the actin cytoskeleton and therefore is influenced by the activity of LIMKs(Scott and Olson,2007).Recent reports discussed in this perspective shed light on the potential role of LIMK in hippocampal dendritic spines and photoreceptor presynaptic terminals and illustrate the importance of LIMK in nerve cell function.

关键词： function. plasticity potential

Optic neuropathy and increased retinal glial fibrillary acidic protein due to microbead-induced ocular hypertension in the rabbit

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International Journal of Ophthalmology(English edition) 2016年第12期9卷 1732-1739页

作者： Jun Zhao Tian-Hui Zhu Wen-Chie Chen Shi-Ming Peng Xiao Sheng Huang Kin-Sang Cho Dong Feng Chen Guer-Sheung Liu School of Ophthalmology & Optometry Affiliated to Shenzhen University Shenzhen 518040 Guangdong Province China Shenzhen eye Hospital Affiliated to Jinan University Shenzhen Key Laboratory of Ophthalmology Shenzhen 518040 Guangdong Province China Department of Ophthalmology Schepens Eye Research Institute Massachusetts Eye and Ear Harvard Medical School Boston 02114 USA Centre for eye research Australia Royal Victorian Eye and Ear Hospital East Melbourne 3002 Australia Ophthalmology Department of Surgery University of Melbourne East Melbourne 3002 Australia

AIM： To characterize whether a glaucoma model with chronic elevation of the intraocular pressure （IOP） was able to be induced by anterior chamber injection of microbeads in ***： In order to screen the optimal dose of microbead injection, IOP was measured every 3d for 4wk using handheld applanation tonometer after a single intracameral injection of 10 μL, 25 μL, 50 μL or 100 μL microbeads （5×10^6 beads/mL; n=6/group） in New Zealand White rabbits. To prolong IOP elevation, two intracameral injections of 50 μL microbeads or phosphate buffer saline （PBS） were made respectively at days 0 and 21 （n=24/group）. The fellow eye was not treated. At 5wk after the second injection of microbeads or PBS, bright-field microscopy and transmission electron microscopy （TEM） were used to assess the changes in the retina. The expression of glial fibrillary acidic protein （GFAP） in the retina was evaluated by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot at 5wk after the second injection of ***： Following a single intracameral injection of 10 μL, 25 μL, 50 μL or 100 μL microbead, IOP levels showed a gradual increase and a later decrease over a 4wk period after a single injection of microbead into the anterior chamber of rabbits. A peak IOP was observed at day 15 after injection. No significant difference in peak value of IOP was found between 10 μL and 25 μL groups （17.13±1.25 mm Hg vs 17.63±0.74 mm Hg; P=0.346）. The peak value of IOP from 50 μL group （23.25±1.16 mm Hg） was significantly higher than 10 μL and 25 μL groups （all P〈0.05）. Administration of 100 μL microbead solution （23.00±0.93 mm Hg） did not lead to a significant increase in IOP compared to the 50 μL group （P=0.64）. A prolonged elevated IOP duration up to 8wk was achieved by administering two injections of 50 μL microbeads （20.48±1.21 mm Hg vs 13.60±0.90 mm Hg in PBS-injected group; P〈0.05）. The bright-field and TEM were used to assess the changes of retinal

关键词： microbead ocular hypertension optic neuropathy glial fibrillary acidic protein rabbit

Absence of ephrin-A2/A3 increases retinal regenerative potential for Müller cells in Rhodopsin knockout mice

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Neural Regeneration research 2021年第7期16卷 1317-1322页

作者： Rui-Lin Zhu Yuan Fang Hong-Hua Yu Dong FChen Liu Yang Kin-Sang Cho Department of Ophthalmology Peking University First HospitalBeijingChina schepens eye research institute Massachusetts Eye and EarHarvard Medical SchoolBostonMAUSA Department of Ophthalmology and Visual Science Eye&ENT HospitalShanghai Medical CollegeFudan UniversityShanghaiChina Guangdong eye institute Department of OphthalmologyGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong ProvinceChina

Müller cells(MC) are considered dormant retinal progenitor cells in *** studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and *** remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of *** we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller *** this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in *** level of ephrin As/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of ***, we investigated the proliferation in primary MC cultures isolated from wild-type and A2~(–/–) A3~(–/–) mice by 5-ethynyl-2′-deoxyuridine(EdU) *** detected a significant increase of EdU~+ cells in MC derived from A2~(–/–) A3~(–/–) ***, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout(Rho~(–/–)) *** further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2~(–/–) A3~(–/–), Rho~(–/–) and Rho~(–/–) A2~(–/–) A3~(–/–) mice and the numbers of EdU~+ cells distributed among different layers of the *** As/EphA4 expression was upregulated in the retina of Rho~(–/–) mice compared to the wild-type *** addition, cultured MC derived from ephrin-A2~(–/–) A3~(–/–) mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type ***, we detected a significant increase of EdU~+ cells in the retinas of adult ephrin-A2~(–/–) A3~(–/–) mice mainly in the inner nuclear layer;and these EdU~+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from

关键词： endogenous stem cell EphA4 ephrin-A2 ephrin-A3 ephrins Müller cell photoreceptor cell regeneration retinal degeneration retinal regeneration retinal stem cell

Task sharing: situation analysis about capacity and resources for management of diabetic retinopathy in Pakistan

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International Journal of Ophthalmology(English edition) 2019年第5期12卷 809-814页

作者： Mufarriq Shah Ayesha Noor C Alex Harper Jill Elizabeth Keeffe Pakistan institute of Community Ophthalmology Hayatabad Medical Complex Vision and Dental Care Clinic Centre for eye research Australia Department of OphthalmologyUniversity of Melbourneand Royal Victorian Eye and Ear Hospital LV Prasad eye institute

AIM: To assess the capacity and resources of eye care facilities, using the WHO Health Systems Framework, to manage diabetic retinopathy(DR) through task ***: Using purposive sampling, four participants(administrators) from four selected hospitals in two provinces in Pakistan were recruited for this cross-sectional study. A survey, to assess the capacity and resources of the selected eye care facilities for the feasibility to adopt task sharing in management of DR to prevent vision loss, was emailed to participants who were asked to complete. Responses to open-ended questions were entered into a Microsoft Excel spread sheet and inductive approach was applied for ***: All the surveyed eye care facilities offer eye care services for people with diabetes and DR. All surveyed eye care facilities have a shortage in the number of human resources across all cadres. Optometrists and mid-level eye care workers did not have active roles in DR screening and management in all four hospitals. All the hospitals surveyed did not have a computerized record management system for patients who visit ophthalmologists for eye examinations. Equipment for detection and management of DR were short in number and main users were ophthalmologists. There was no policy for population-based screening program for detection of DR in any of the surveyed ***: A system-based approach to manage DR is needed. The capacity of eye care facilities and the potential to improve access of people with diabetes to eyecare services can be enhanced through implementation of task sharing.

关键词： task sharing capacity diabetes diabetic retinopathy Pakistan