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Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

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Neural Regeneration Research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and Stem cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore department of Cornea and External eye Disease Singapore National Eye CenterSingapore ophthalmology and Visual Sciences Academic Clinical Program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

Conservation and divergence of Grb7 family of Ras-binding domains

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Protein & cell 2012年第1期3卷 60-70页

作者： Raju V.S.Rajala Ammaji Rajala Vivek K.Gupta department of ophthalmology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA department of cell biology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA dean A.mcgee eye institute Oklahoma CityOK 73104USA

Ras proteins are signal-transducing GTPases that cycle between inactive GDP-bound and active GTP-bound *** is a prolific signaling molecule interacting with a spectrum of effector molecules and acting through more than one signaling *** Ras-effector proteins contain a Ras-associating(RA)domain through which these associate with Ras in a GTP-dependent *** RA domain is highly conserved among the members of the growth factor receptor-bound(Grb)7 family of proteins which includes Grb7,Grb10 and *** laboratory has reported an unusual observation that RA domain of Grb14 binds to the C-terminal nucleotide binding site of cyclic nucleotide gated channel(CTRCNGA1)and inhibits the channel *** modeling of the CTR-CNGA1 displays 50%---70%tertiary structural similarity towards Ras *** named this region as Ras-like domain(RLD).The interaction between RA-Grb14 and RLD-CNGA1 is mediated through a simple protein-protein interaction temporally and spatially regulated by light and *** is interesting to note that Grb14 binds to GTPase-mutant Rab5,a Ras-related small GTPase whereas Grb10 binds only to GTP-bound form of active Rab5 but not to GTPase-defective mutant *** results suggest that Grb14 might have been evolved later in the evolution that binds to both Ras and nucleotide binding proteins such as *** studies also suggest that eukaryotic CNG channels could be evolved through a gene fusion between prokaryotic ion channels and cyclic nucleotide binding proteins,both of which might have undergone several sequence variations for functional adaptation during evolution.

关键词： growth factor receptor-bound protein 14 Ras-associating domain cyclic nucleotide gated channel rod outer segments tyrosine kinase signaling Ras proteins

Coagulase-negative Staphylococci in Conjunctivitis and Blepharitis

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眼科学报 1993年第3期9卷 129-135页

作者： Yue-Kong Au Harold GJensen James Rowsey Mark Reynolds department of ophthalmology Louisiana State UniversityShreveportLouisianaUSA dean mcgee eye institute Oklahoma CityOklahomaUSA

Coagulase-negative staphylococcus(C-NS)are regarded as normal flora of the lids and *** ability of these organisms to cause conjunctivitis and blepharitis can be overlooked or *** elucidate the role of individual C-NS species in these eye diseases we compared Staphylococcus *** from the conjunctiva and lids of 50 healthy volunteers with 248 strains of Staphylococcus isolated from patients with staphylococcal conjunctivitis or *** was the most frequent species isolated from the conjunctiva and lids of both *** was isolated only from infected *** individual C-NS species was found to be significantly associated with eye disease,but the colony count of C-NS after isolation was a useful indicator of conjunctivitis and *** ability of Staphylococcus to ferment mannitol or mannose was associated with isolates only from infected patients.

关键词： Staphylococcus aureus coagulase-negative Staphylococcus Staphylococcus epidermidis conjunctivitis blepharitis

Mechanism involved in the modulation of photoreceptor-specific cyclic nucleotidegated channel by the tyrosine kinase adapter protein Grb14

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Protein & cell 2011年第11期2卷 906-917页

作者： Vivek K.Gupta Ammaji Rajala Karla K.Rodgers Raju V.S.Rajala department of ophthalmology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA department of cell biology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA department of Biochemistry and Molecular biology University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA dean A.mcgee eye institute University of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA

We recently found that growth factor receptor-bound(Grb)protein 14 is a novel physiological modulator of photoreceptor specific cyclic nucleotide-gated channel alpha subunit(CNGA1).Grb14 promotes the CNG channel closure through its Ras-associating(RA)*** the current study we show that this RA domain-mediated inhibition of rod CNG channel is electrostatic in ***14 competes with cGMP for the CNGA1 binding pocket and electrostatically interacts with Arg^(559) through a negatively chargedβ-turn at its RA ***,the three Glu residues(180–182)in Grb14 are absolutely critical for electrostatic interaction with the cGMP binding pocket and resultant *** study also demonstrates that substitution of Lys^(140) for Ala or in combination with polyglutamte mutants of Grb14 results in a significantly reduced binding with *** results suggest that in addition to Glu^(180–182) and Lys^(140),other residues in Grb14 may be involved in the electrostatic interaction with *** RA domain is highly conserved among the members of Grb7 family of proteins,which includes Grb7,Grb10 and ***,only Grb14 is able to modulate the channel activity,but not Grb7 and *** together,it suggests the existence of a divergence in RA domains among the members of the Grb7 family.

关键词： growth factor receptor-bound protein 14(Grb14) Ras-associating domain cyclic nucleotide gated channel rod outer segments tyrosine kinase signaling

Neuroprotective role of protein tyrosine phosphatase-1B in rod photoreceptor neurons

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Protein & cell 2013年第12期4卷 890-892页

作者： Raju V.S.Rajala Ammaji Rajala department of ophthalmology University of Oklahoma Health Sciences CenterOklahoma CityOklahoma 73104USA department of Physiology University of Oklahoma Health Sciences CenterOklahoma CityOklahoma 73104USA department of cell biology University of Oklahoma Health Sciences CenterOklahoma CityOklahoma 73104USA dean A.mcgee eye institute Oklahoma CityOklahoma 73104USA

Dear Editor,Protein tyrosine phosphatase-1B(PT-P1B)is an abundant,widely expressed non-receptor tyrosine phosphatase,which is thought to be a key negative regulator of insulin signaling(Tonks,2003).Increased and prolo... 详细信息

关键词： PTP1B insulin of

Use of a handheld slit beam intraoperatively to assist in big bubble formation during deep anterior lamellar keratoplasty

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Annals of eye Science 2018年第1期3卷 369-374页

作者： Alexander S.Davis Peter Bedard Joshua H.Hou department of ophthalmology and Visual Neurosciences University of MinnesotaMinneapolisMNUSA dean mcgee eye institute Oklahoma CityOKUSA Lions Gift of Sight eye Bank St.PaulMNUSA

Deep anterior lamellar keratoplasty(DALK)is preferred over conventional penetrating keratoplasty(PKP)for the treatment of anterior corneal opacities or ectasias due to decreased risk of endothelial ***,DALK remains surgically challenging,largely due to challenges associated with achieving consistent pneumo-dissection of posterior stroma from the underlying pre-Descemet’s or Descemet’s membrane(DM).Air must be injected at sufficient depth in the corneal stroma in order to achieve successful pneumo-dissection,but advancing a needle too deep into the cornea can lead to perforation of *** describe here a novel technique using a handheld slit lamp(Eidolon model 510L,Eidolon Optical LLC,Natick,MA,USA)to assist in creation of the big-bubble in DALK *** of a handheld slit beam intraoperatively is a safe,relatively inexpensive,and effective technique for increasing the success of big-bubble formation in DALK procedures.

关键词： Deep anterior lamellar keratoplasty(DALK) big bubble technique slit beam

The molecular chaperone Hsp90α deficiency causes retinal degeneration by disrupting Golgi organization and vesicle transportation in photoreceptors

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Journal of Molecular cell biology 2020年第3期12卷 216-229页

作者： Yuan Wu Xiudan Zheng Yubo Ding Min Zhou Zhuang Wei Tao Liu Kan Liao Key Laboratory of Systems biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China department of ophthalmology Eye and ENT Hospital of Fudan UniversityShanghai 200031China

Heat shock protein 90(Hsp90)is an abundant molecular chaperone with two isoforms,Hsp90α and ***90β deficiency causes embryonic lethality,whereas Hsp90α deficiency causes few abnormities except male *** this paper,we reported that Hsp90α was exclusively expressed in the retina,testis,and *** deficiency caused retinitis pigmentosa(RP),a disease leading to *** Hsp90α-deficient mice,the retina was deteriorated and the outer segment of photoreceptor was *** staining and electron microscopic analysis revealed disintegrated Golgi and aberrant intersegmental vesicle transportation in Hsp90α-deficient *** analysis identified microtubule-associated protein IB(MAP1B)as an Hsp90α-associated protein in *** deficiency increased degradation of MAP1B by inducing its ubiquitination,causing a-tubulin deacetylation and microtubule ***,the treatment of wild-type mice with 17-DMAG,an Hsp90 inhibitor of geldanamycin derivative,induced the same retinal degeneration as Hsp90α *** together,the microtubule destabilization could be the underlying reason for Hsp90α deficiency-induced RP.

关键词： Hsp90α retinitis pigmentosa Golgi disintegration vesicle transportation MAP1B acetylatedα-tubulin microtubule cytoskeleton

Identification, quantification and agerelated changes of human trabecular meshwork stem cells

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eye and Vision 2019年第1期6卷 261-270页

作者： Yogapriya Sundaresan Muthukkaruppan Veerappan Krishnadas Subbiah Ramasamy Gowri Priya Chidambaranathan department of Immunology and Stem cell biology Aravind Medical Research FoundationMaduraiTamil NaduIndia. Glaucoma Clinic Aravind Eye Hospital and Post Graduate Institute of OphthalmologyMaduraiTamil NaduIndia

Background:Loss of cells in the human trabecular meshwork(TM)has been reported with ageing and in *** study aims to identify,quantify and determine the age-related changes of human TM stem cells(TMSCs).Methods:Isolation of TM cells/paraffin sectioning was carried out using human corneoscleral rings and whole *** TM cells/sections were immunostained for the stem cell markers ATP-binding cassette protein G2(ABCG2),nerve growth factor receptor p75 and AnkyrinG(AnkG).Images were acquired using Leica SP8 confocal *** isolated cells were analyzed for two parameters-ABCG2 expression and nucleus to cytoplasmic ratio(N/C ratio).The total number of TM cells and those positive for ABCG2 and p75 in each section were *** rank order correlation was used to determine the association between age and the cell ***:The TMSCs were identified based on two parameters-high ABCG2 expression and high N/C ratio>*** stem cells were also positive for p75 and *** TMSC content based on the two parameters was 21.0±1.4%in60 *** stem cells with high ABCG2 and p75 expression were restricted to the Schwalbe’s line region of the TM.A significant correlation was observed between the reduction in TMSC content and TM cell count during ***:The human TMSCs were identified and quantified based on two parameter *** study established a significant association between age-related reduction in TMSC content and TM cell loss.

关键词： Human trabecular meshwork Trabecular meshwork stem cells Two-parameter analysis Age-related changes Primary open angle glaucoma

Effect of integrin α5β1 inhibition on SDF-l/CXCR4-mediated choroidal neovascularization

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International Journal of ophthalmology(English edition) 2018年第5期11卷 726-735页

作者： Yang Lyu Wen-Qin Xu Li-Juan Sun Xiao-Yan Pan Jian Zhang Yu-Sheng Wang department of ophthalmology Eye Institute of China PLAXijing Hospitalthe Fourth Military Medical University department of ophthalmology General Hospital of Lanzhou Military Command department of Biochemistry and Molecular biology the Fourth Military Medical University

AIM：To investigate the roles of integrins in choroidal neovascularization（CNV） and their associations with the stromal cell-derived factor-1（SDF-1）/CXCR4 ***：CNV lesions were induced in mice using laser *** CNV induction,all animals were randomly assigned to：control,SDF-1,SDF-1＋age-related macular degeneration（AMD） 3100（CXCR4 inhibitor）,and SDF-1＋ATN161（integrin α5β1 inhibitor） groups;their effects on CNV progression were observed using hematoxylin eosin（HE） staining,fundus fluorescein angiography（FFA） grading and optical coherence tomography（OCT）,and their effects on CXCR4/integrin α5 expression were evaluated using Western blot and double immunofluorescence ***-exposed endothelial cells（ECs） were used to simulate CNV in vitro,they were treated with SDF-1,combined with CXCR4 siRNA/AMD3100 or ATN161,and expression of integrin α5,cell migration and tube formation were ***：Integrin subunit α5 increased at 3^ rd and 7^ th day and decreased at 14 ^th day in CNV mice,with no significant change of β***4 expression in CNV mice had persistent increase within 14 d after ***-1 treatment significantly promoted the CNV progression during 3-14 *** mean CNV length in AMD3100 andATN161 group at day 7 was 270.13 and 264.23 μm in HE images,significantly lower than the mean length in SDF-1（345.70 μm） ***3100 and ATN161 also significantly reduced thickness and leakage of CNV induced by *** integrin α5 positive area in SDF-1 group reached 2.31×104 μm^2,significantly higher than control（1.25×104 μm^2）,which decreased to 1.78×104 μm^2 after AMD3100 *** 61.36% of ECs in CNV lesions expressed α5 in SDF-1 group,which significantly decreased to 43.12% after AMD3100 *** vitro,integrin α5 peaked by 6 folds after 6 h of hypoxia exposure and CXCR4 gradually increased by up to 2.3 folds after 24 h of *** 25.12% of ECs expressed integrin α5 after SDF-1 stimulation,which

关键词： choroidal neovascularization endothelial cells stromal cell-derived factor-1 CXCR4 integrin α5β1 hypoxia