1.Research progress of mitochondrial unfolded protein response in eye diseases
Liang GU ; Pengfei LI ; Huaijin GUAN ; Min JI
International Eye Science 2025;25(9):1425-1430
The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.
2.Epidemiological survey of eye diseases in the predisease stage
Recent Advances in Ophthalmology 2024;44(3):169-172
Epidemiologic study is an essential scientific basis for disease prevention,intervention and health policy making.Predisease often refers to the abnormal state found in epidemiologic study/screening,which has not yet reached the diagnostic criteria for the disease.It is the"in-between"state from a healthy state to a diseased state;if not intervened properly,it will develop into a disease.Predisease includes precancerous lesions,prediabetes,prehypertension,as well as eye diseases in the predisease stage,such as premyopia,preglaucoma and ocular complications of prediabetes.Proper in-tervention in predisease,when no clinical manifestations were found,or the very early stage can prevent the occurrence of diseases.However,ophthalmologists have not paid enough attention to the epidemiologic study of eye diseases in the pre-disease stage and have known little about how to conduct the epidemiologic study.Herein,this paper discussed the epide-miologic study of several common eye diseases with high prevalence and significant visual impairment in the predisease sta-ges based on experience in the relevant field.
3.Research progress of gut microbiota in ophthalmic diseases
Qianyi SHEN ; Huaijin GUAN ; Min JI
Chinese Journal of Experimental Ophthalmology 2024;42(6):584-586
In recent years, research on gut microbiota has been increasing.Multiple studies have shown that the dysbiosis of gut microbiota plays a key role in the occurrence and development of various diseases, potentially revealing a new target for disease prevention and treatment intervention.This article reviews the role of gut microbiota in the pathogenesis and treatment of ophthalmic diseases, including autoimmune uveitis, age-related macular degeneration, diabetic retinopathy, primary open-angle glaucoma and Sj?gren syndrome, etc.The mechanism of ocular tissue damage may be the imbalance of the gut microbiota affects microbial metabolites such as butyrate, which influences the intestinal epithelial cell barrier, or mediates immune responses.Investigating the role of gut microbiota dysbiosis in the development and progression of ocular diseases may improve our understanding of the mechanisms of related diseases.Regulation of the gut microbiota or modulation of the metabolites may be a potential way to treat certain eye diseases.It provides new ideas for further exploration of the pathogenesis and adjuvant treatment of such eye diseases.
4.Effects of Nei endonuclease Ⅷ-like protein 1 on H2O2-induced apoptosis and autophagy in lens epithelial cells
Sijie BAO ; Pengfei LI ; Lihua KANG ; Congyu WANG ; Siwen WANG ; Huaijin GUAN
Recent Advances in Ophthalmology 2023;43(12):934-939
Objective To investigate the influence of Nei endonuclease Ⅷ-like protein 1(NEIL1)on H2O2-induced apoptosis and autophagy in lens epithelial cells(LECs).Methods Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression of NEIL1 messenger ribonucleic acid(mRNA)in the anterior lens capsule and LEC line SRA01/04 cells from age-related cataract(ARC)patients and macular epiretinal membrane patients who underwent the clear lens extraction.SRA01/04 cells were then divided into the control group,OE-Vector group and OE-NEIL1 group.RT-PCR and Western blot(WB)were used to detect the overexpression efficiency.Subsequently,the cells were divided into the control group,H2O2 group,OE-Vector H2O2 group and OE-NEIL1 H2O2 group;cell viability was detected by Cell Count-ing Kit-8,WB was used to evaluate the expression of autophagy-related proteins(ATG7,P62,Beclinl,LC3-Ⅰ and LC3-Ⅱ)and apoptosis-related proteins(Bax and Bcl-2),and fluorescent staining was adopted to measure cell apoptosis and mito-chondrial membrane potential.Results The expression of NEIL1 mRNA in the anterior lens capsule samples from ARC patients was significantly lower than that of macular epiretinal membrane patients,and the expression of NEIL1 mRNA in the SRA01/04 cells in the H2O2 group was also lower than that in the control group(both P<0.05).The results of RT-PCR and WB revealed that the expressions of NEIL1 mRNA and protein in the SRA01/04 cells of the OE-NEIL1 group were signif-icantly higher than those in the OE-Vector group(both P=0.000).Compared with the control group,the viability of SRA01/04 cells in the H2O2 group decreased,the expression of the Bax protein was up-regulated,the Bcl-2 protein was down-regulated,viable cells labeled with Mito-Tracker decreased,and apoptotic cells labeled with Annexin V-FITC in-creased,with statistical significances(all P<0.05).Compared with the OE-Vector H2O2 group,in the OE-NEIL1 H2O2 group,the viability of SRA01/04 cells significantly improved,the autophagy-related proteins(ATG7,P62,Beclin1,LC3-Ⅰand LC3-Ⅱ)and Bcl-2 protein were significantly up-regulated,the Bax protein was down-regulated,viable cells marked with Mito-Tracker increased,and apoptotic cells labeled with Annexin V-FITC decreased(all P<0.05).Conclusion Under the oxidative stress induced by H2O2,NEIL1 can promote autophagy of LECs,maintain homeostasis of LECs,and then increase cell viability and reduce apoptosis of LECs,participating in the occurrence and development of ARC.
5.Research progress of the peripapillary intrachoroidal cavitation
Lijuan ZHAO ; Jiawei LUO ; Mengjia TAN ; Yan MENG ; Shu LIANG ; Min JI ; Huaijin GUAN
Recent Advances in Ophthalmology 2023;43(12):1001-1004
Peripapillary intrachoroidal cavitation(PICC)is a common fundus lesion in high myopia.The typical mani-festation of PICC in fundus color photography is orange lesions with clear boundaries,which often occur below the myopic arc,and a weak reflection cavity in the choroid in optical coherence tomography(OCT).With the development and wide-spread application of OCT technology,researchers have gained a clearer understanding of the imaging features,pathogene-sis and clinical significance of PICC.This article introduces the definition,imaging features,pathogenesis,and relationship with glaucoma of PICC to provide new ideas for further elucidating the pathogenesis and clinical significance of PICC.
6.Research progress on regulation of lncRNA in age-related ophthalmopathy
Chinese Journal of Experimental Ophthalmology 2022;40(10):992-995
Long non-coding RNA (lncRNA) is a class of transcripts longer than 200 nucleotides, which do not have the function of coding proteins.Widely involved in the progress of various human diseases, lncRNA has become a new research hotspot and the regulatory role of it has been paid more and more attention.Studies in recent years found that lncRNA is abnormally expressed in age-related macular degeneration (AMD) and age-related cataract (ARC) compared with healthy individuals.LncRNA ZNF503-AS1, BANCR and MEG3 can play important roles in regulating function of retinal pigment epithelial cell, which can lead to the development of AMD.LncRNA MIAT, TUG1 and H19 can have important regulatory effects through competitive binding with microRNAs, thus affecting the occurrence and development of ARC.This article reviewed the research progress of lncRNA in the AMD and ARC related field, revealed the role of different lncRNAs in the diseases, provided a new perspective for elucidating the mechanism of the diseases and found a new biomarker for the diagnosis and treatment of the diseases.
7.Paying close attention to the impact of cataract phacoemulsification surgery on ocular tissue
Chinese Journal of Experimental Ophthalmology 2021;39(4):273-279
Although phacoemulsification is quite minimally invasive, effective and safe, it can still injure the structure of eyes and cause and/or aggravate posterior vitreous detachment, retinal detachment, macular edema, diabetic vitreoretinopathy, age-related macular degeneration and high myopic retinopathy due to the turbulence of operation and instrument to intraocular tissue, which disturbs the stability of anterior chamber and vitreous body, damages blood-ocular barrier and results in the release of inflammatory cytokines.Ophthalmologists should have a thorough understanding of relevant knowledge to emphasize the operating risk evaluation and management in perioperative period in order to control the energy and operation time of phacoemulsification as much as possible, especially for the patients with serious fundus diseases and systemic diseases.Ophthalmologist should avoid the operating disturbance of intraocular tissue to the utmost extent by reducing the phacoemulsification energy and duration.It is very important for us to realize the management of whole process of cataract surgery "from anterior segment to posterior segment" and "from eye to whole body" so as to further improve the postoperative visual quality and satisfaction of patients.
8.Feasibility and clinical significance of intraoperative real-time fundus examination in cataractous eyes
Shu SU ; Si WU ; Jian WU ; Yu GUAN ; Yong WANG ; Mei YANG ; Min JI ; Huaijin GUAN
Chinese Journal of Experimental Ophthalmology 2020;38(4):331-335
Objective:To investigate the feasibility of real-time screening and diagnosing fundus diseases with Wild Field Imaging System (WFIS SW-8000) in the eyes with dense cataract patients.Methods:A series of case-observational study was carried out.Ninety-six dense cataractous eyes of 90 patients with suspected fundus diseases were included in Affiliated Hospital of Nantong University from April to July 2019.Lens phacoemulsification combined with intraocular lens implantation was performed after the opacity lens was removed, and fundus examination was performed with WFIS SW-8000.Super field lens, optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) was used to verify the fundus findings after surgery, which were compared with WFIS SW-8000.This study protocol was approved by Ethics Committee of Affiliated Hospital of Nantong University and followed the Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical examination.Results:Among 96 eyes, fundus diseases were detected in 40 eyes with the detection rate of 41.67% by WFIS SW-8000 examination, including dry age-related macular degeneration (AMD) in 2 eyes, wet AMD in 3 eyes, polypoidal choroidal vasculopathy (PCV) in 1 eye, high myopia retinopathy (HMR) in 7 eyes, central retinal vein occlusion (CRVO) with macular edema (ME) in 1 eye, mild non-proliferative diabetic retinopathy (NPDR) in 12 eyes, moderate NPDR in 7 eyes, severe NPDR in 4 eyes and proliferative diabetic retinopathy (PDR) in 3 eyes.Fundus diseases were detected in 45 eyes with detection rate of 46.88% after surgery by a super field lens, OCT and FFA.The detectable rate of digital retinal camera examination and super field lens, OCT and FFA showed no significant difference between intraoperation and postoperation (χ 2=0.528, P=0.468). Twenty-two eyes with fundus neovascular disease or macular edema requiring drug intervention were identified intraoperatively, and intravitreal anti-inflammatory and/or anti-vascular endothelial growth factor (VEGF) drugs were injected in 11 eyes during the operation. Conclusions:WFIS SW-8000 is a useful tool for the accurate and convenient method in real-time fundus examination during phacoemulsification, which is feasible and helpful for timely intervention in and treatment of fundus diseases.
9.NLRP3 inflammasome and eye diseases
Yujian ZHANG ; Min JI ; Huaijin GUAN
Chinese Journal of Experimental Ophthalmology 2020;38(4):365-368
Nucleotide binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a set of intracellular protein complexes.NLRP3 inflammasome can trigger the activation of caspase-1 and contribute to the maturation of interleukin, and finally result in a series of inflammation responses in host.Inflammasomes are activated in a variety of cases, including multiple inflammation-related eye diseases, such as xerophthalmia, glaucoma, age-related macular degeneration and so on.This article aimed to interpret the effect and mechanism of the activation of NLRP3 inflammasome, and reviewed how the mutation of gene or the structure disturbance of protein related to NLRP3 inflammasome affects the occurrence and development of inflammation-related eye diseases.
10.Prevalence and associated factors for pterygium in rural people aged 50 years and above in Funing County,Jiangsu Province
Junfang ZHANG ; Mei YANG ; Rongrong ZHU ; Bai QIN ; Haihong SHI ; Lihua KANG ; Jian SHI ; Nan HU ; Huaijin GUAN
Chinese Journal of Experimental Ophthalmology 2019;37(3):212-217
Objective To investigate the prevalence and associated risk factors for pterygium among people aged 50 years and above in Funing County,Jiangsu Province.Methods A cluster random sampling method was performed,the subjects aged 50 years or above were randomly selected from 30 survey sites in Funing County,Jiangsu Province.Questionnaires,visual acuity tests,the examinations of eye surface,anterior segment,fundus examinations were conducted.Pterygium was diagnosed and graded clinically by slit lamp examination.The risk factors were acquired from questionnaires and analyzed by the multivariate logistic regression analysis.This study protocol was approved by Ethic Committee of Affiliated Hospital of Nantong University (NO.2010-05).Written informed consent was obtained from each subject prior to entering study cohort.Results A total of 6 145 persons aged 50 years and above were enumerated,and actually 5 947 (96.8%) participants were examined.Among them,1 950 cases were diagnosed as pterygium in either eye and 1 228 cases were diagnosed as pterygium in binoculus,which was equivalent to the 32.79% [95% confidence interval(CI):31.60%-33.98%] of pterygium in either eye and 20.65% (95% CI:19.62%-21.68%) in bilateral pterygium.Among 2467 male subjects,838 were diagnosed as pterygium (33.97%,95% CI:32.10%-35.84%).Among 3480 female subjects,1 112 were diagnosed as pterygium (31.95%,95% CI:30.40%-33.51%).There was no significant difference in the prevalence of pterygium between genders (P =0.135).Multivariate Logistic analysis showed that,older age (50 ~ <60 years:odds ratio [OR] =1.00;60 ~ <70 years:OR=1.54,P<0.001;70 ~ <80 years,OR=1.83,P<0.001;≥80 years:OR=1.99,P<0.001),low educational level (no education:OR =1.00;<primary:OR =0.87,P =0.031;primary education:OR =0.72,P =0.002;≥ secondary education:OR =0.63,P =0.002),farmer occupations (OR =1.34,P =0.020),and long outdoor work time (OR =1.13,P =0.026) were independent risk factors for pterygium.Gender,marriage,income,hypertension,diabetes,smoking and alcohol use history were not associated with pterygium (all at P>0.05).Conclusions The prevalence of pterygium in Funing County is 32.79% in people aged 50 years and above.The high prevalence of pterygium may be associated with older age,low education level and long outdoor work time.

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