novel-micropulse-transscleral-cyclophotocoagulation-system-for

Novel Micropulse Transscleral Cyclophotocoagulation System for Clinical Treatment of Refractory Glaucoma

Traditional transscleral cyclophotocoagulation has been established as an effective intervention for refractory glaucoma. While demonstrating therapeutic ...

Nanjing Medical University

Excessive light exposure leads to retinal degeneration and accelerates the progression and severity of several ocular diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa. Long non-coding RNAs (LncRNAs) have emerged as important regulators of photoreceptor development and ocular diseases. In this study, we investigated the role of lncRNA-MEG3 in light-induced retinal degeneration. MEG3 expression was significantly up-regulated after light insult in vivo and in vitro. MEG3 silencing protected against light-induced retinal degeneration in vivo and light-induced photoreceptor cell apoptosis in vitro. Mechanistically, MEG3 regulated retinal photoreceptor cell function by acting as p53 decoy. MEG3 silencing decreased caspase 3/7 activity, up-regulated anti-apoptotic protein (Bcl-2) expression, and down-regulated pro-apoptotic protein (Bax) expression. Taken together, this study provides a promising method of MEG3 silencing for treating light-induced retinal degeneration.

Long non-coding RNA MEG3 silencing protects against light-induced retinal degeneration.

VEGF-induced neovascularization plays a pivotal role in corneal neovascularization (CoNV). The current study investigated the potential effect of ginsenoside Rh2 (GRh2) on neovascularization. In HUVECs, pretreatment with GRh2 largely attenuated VEGF-induced cell proliferation, migration, and vessel-like tube formation in vitro. At the molecular level, GRh2 disrupted VEGF-induced VEGF receptor 2 (VEGFR2)-Grb-2-associated binder 1 (Gab1) association in HUVECs, causing inactivation of downstream AKT and ERK signaling. Gab1 knockdown (by targeted short hairpin RNA) similarly inhibited HUVEC proliferation and migration. Notably, GRh2 was ineffective against VEGF in Gab1-silenced HUVECs. In a mouse cornea alkali burn model, GRh2 eyedrops inhibited alkali-induced neovascularization and inflammatory cell infiltrations in the cornea. Furthermore, alkali-induced corneal expression of mRNAs/long noncoding RNAs in cornea were largely attenuated by GRh2. Overall, GRh2 inhibits VEGF-induced angiogenic effect via inhibiting VEGFR2-Gab1 signaling in vitro. It also alleviates angiogenic and inflammatory responses in alkali burn-treated mouse corneas.-Zhang, X.-P., Li, K.-R., Yu, Q., Yao, M.-D., Ge, H.-M., Li, X.-M., Jiang, Q., Yao, J., Cao, C. Ginsenoside Rh2 inhibits vascular endothelial growth factor-induced corneal neovascularization.

Ginsenoside Rh2 inhibits vascular endothelial growth factor-induced corneal neovascularization.

Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown.

Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease.

Antibody-based therapy is an effective strategy for treating ocular angiogenesis. However, short-acting efficacy and poor treatment compliance usually occurs in clinical practices. Thus, it is required to develop a drug delivery system to improve the bioavailability and decrease the toxicity of anti-angiogenic antibody. Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF). In this study, bevacizumab was encapsulated into poly (lactide-co-glycolide) (PLGA) nanoparticles. PLGA encapsulation could prolong the residency of bevacizumab in the vitreous and aqueous humor and produce long-lasting drug concentrations. Bevacizumab-encapsulated PLGA had no significant cytotoxicity and tissue toxicity effect in vitro and in vivo. In vitro studies showed that bevacizumab-encapsulated PLGA was more effective than bevacizumab in inhibiting VEGF-mediated endothelial cell proliferation, migration and tube formation. In vivo studies showed that bevacizumab-encapsulated PLGA enhanced the anti-angiogenic efficiency of bevacizumab for treating corneal neovascularization and retinal neovascularization. Thus, bevacizumab-encapsulated PLGA could increase the bioavailability and decrease the toxicity of bevacizumab during ocular angiogenesis therapy.

Effect of nanoencapsulation using poly (lactide-co-glycolide) (PLGA) on anti-angiogenic activity of bevacizumab for ocular angiogenesis therapy.

Proliferative vitreoretinopathy (PVR) is one of the major challenges in retinal surgery, which occurs in the patient with complex retinal surgery or penetrating eye injury. Circular RNAs (circRNAs) have emerged as important regulators in many biological processes and disease development. However, the characterization and function of circRNAs in PVR remains elusive. In this study, we identified 91 dysregulated circRNAs in the epiretinal membranes (ERMs) of PVR patients. We further investigated the expression pattern of circ_0043144. circ_0043144 was significantly up-regulated in the vitreous samples and the corresponding serum samples of the patients with PVR. circ_0043144 expression was significantly down-regulated after PVR operation. In vitro studies revealed that circ_0043144 was involved in the regulation of the proliferation, migration and secretion ability of ARPE-19 cells, which is critical for ERM formation. Collectively, this study indicates that circRNAs are potential regulators of the pathogenesis of PVR. circ_0043144 is a promising prognostic and diagnostic indicator for PVR diseases.

Comprehensive circular RNA profiling of proliferative vitreoretinopathy and its clinical significance.

The crosstalk between vascular pericytes and endothelial cells (ECs) is critical for microvascular stabilization and remodeling; however, the crosstalk is often disrupted by diabetes, leading to severe and even lethal vascular damage. Circular RNAs are a class of endogenous RNAs that regulate several important physiological and pathological processes. Here we show that diabetes-related stress up-regulates cPWWP2A expression in pericytes but not in ECs. In vitro studies show that cPWWP2A directly regulates pericyte biology but indirectly regulates EC biology via exosomes carrying cPWWP2A. cPWWP2A acts as an endogenous miR-579 sponge to sequester and inhibit miR-579 activity, leading to increased expression of angiopoietin 1, occludin, and SIRT1. In vivo studies show that cPWWP2A overexpression or miR-579 inhibition alleviates diabetes mellitus-induced retinal vascular dysfunction. By contrast, inhibition of cPWWP2A-mediated signaling by silencing cPWWP2A or overexpressing miR-579 aggravates retinal vascular dysfunction. Collectively, this study unveils a mechanism by which pericytes and ECs communicate. Intervention of cPWWP2A or miR-579 expression may offer opportunities for treating diabetic microvascular complications.

Targeting pericyte-endothelial cell crosstalk by circular RNA-cPWWP2A inhibition aggravates diabetes-induced microvascular dysfunction.

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Vascular pericyte degeneration is the predominant clinical manifestation of DR, yet the mechanism governing pericyte degeneration is poorly understood. Circular RNAs (circRNAs) play important roles in multiple biological processes and disease progression. Here, we investigated the role of circRNA in pericyte biology and diabetes-induced retinal vascular dysfunction. cZNF532 expression was upregulated in pericytes under diabetic stress, in the retinal vessels of a diabetic murine model, and in the vitreous humor of diabetic patients. cZNF532 silencing reduced the viability, proliferation, and differentiation of pericytes and suppressed the recruitment of pericytes toward endothelial cells in vitro. cZNF532 regulated pericyte biology by acting as a miR-29a-3p sponge and inducing increased expression of NG2, LOXL2, and CDK2. Knockdown of cZNF532 or overexpression of miR-29a-3p aggravated streptozotocin-induced retinal pericyte degeneration and vascular dysfunction. By contrast, overexpression of cZNF532 or inhibition of miR-29a-3p ameliorated human diabetic vitreous-induced retinal pericyte degeneration and vascular dysfunction. Collectively, these data identify a circRNA-mediated mechanism that coordinates pericyte biology and vascular homeostasis in DR. Induction of cZNF532 or antagonism of miR-29a-3p is an exploitable therapeutic approach for the treatment of DR.

Circular RNA-ZNF532 regulates diabetes-induced retinal pericyte degeneration and vascular dysfunction.

Epigenetic alterations occur in many physiological and pathological processes. N-methyladenosine (mA) modification is the most prevalent modification in eukaryotic mRNAs. However, the role of mA modification in pathological angiogenesis remains elusive. In this study, we showed that the level of mA modification was significantly upregulated in endothelial cells and mouse retinas following hypoxic stress, which was caused by increased METTL3 levels. METTL3 silencing or METTL3 overexpression altered endothelial cell viability, proliferation, migration, and tube formation in vitro. METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization. Mechanistically, METTL3 exerted its angiogenic role by regulating Wnt signaling through the mA modification of target genes (e.g., LRP6 and dishevelled 1 [DVL1]). METTL3 enhanced the translation of LRP6 and DVL1 in an YTH mA RNA-binding protein 1 (YTHDF1)-dependent manner. Collectively, this study suggests that METTL3-mediated mA modification is an important hypoxic stress-response mechanism. The targeting of mA through its writer enzyme METTL3 is a promising strategy for the treatment of angiogenic diseases.

Role of METTL3-Dependent N-Methyladenosine mRNA Modification in the Promotion of Angiogenesis.

The vitreous body is an important part of the ocular body fluid. A foldable capsular vitreous body (FCVB) is designed to treat chronic adverse complications in severe ocular trauma and silicone oil-dependent eyes. This study is aimed at investigating a method for implanting an FCVB, its postoperative efficacy, and clinical value.

Outcomes of a Foldable Capsular Vitreous Body Implantation: A Retrospective Study.

Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization.

Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis.

Pericytes are located in the stromal membrane of the capillary outer wall and contain endothelial cells. They are pivotal in regulating blood flow, enhancing vascular stability, and maintaining the integrity of the blood-retina barrier/blood-brain barrier. The pluripotency of pericytes allows them to differentiate into various cell types, highlighting their significance in vascular disease pathogenesis, as demonstrated by previous studies. This capability enables pericytes to be a potential biomarker for the diagnosis and a target for the treatment of vascular disorders. The retina, an essential part of the eyeball, is an extension of cerebral tissue with a transparent refractive medium. It offers a unique window for assessing systemic microvascular lesions. Routine fundus examination is necessary for patients with diabetes and hypertension. Manifestations, such as retinal artery tortuosity, dilation, stenosis, and abnormal arteriovenous anastomosis, serve as typical hallmarks of retinal vasculopathy. Therefore, studies of ocular vascular diseases significantly facilitate the exploration of systemic vascular diseases.

The role of pericyte in ocular vascular diseases.

To evaluate the efficacy, safety, and outcomes of a blade- and cautery-free surgical protocol for pterygium removal.

Article	Year
Long non-coding RNA MEG3 silencing protects against light-induced retinal degeneration. Biochemical and biophysical research communications\| PubMed ID: 29409883	2018
Ginsenoside Rh2 inhibits vascular endothelial growth factor-induced corneal neovascularization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology\| PubMed ID: 29465315	2018
Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology\| PubMed ID: 29949792	2018
Effect of nanoencapsulation using poly (lactide-co-glycolide) (PLGA) on anti-angiogenic activity of bevacizumab for ocular angiogenesis therapy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 30257317	2018
Comprehensive circular RNA profiling of proliferative vitreoretinopathy and its clinical significance. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 30597308	2019
Targeting pericyte-endothelial cell crosstalk by circular RNA-cPWWP2A inhibition aggravates diabetes-induced microvascular dysfunction. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 30914462	2019
Circular RNA-ZNF532 regulates diabetes-induced retinal pericyte degeneration and vascular dysfunction. The Journal of clinical investigation\| PubMed ID: 32343678	2020
Role of METTL3-Dependent N-Methyladenosine mRNA Modification in the Promotion of Angiogenesis. Molecular therapy : the journal of the American Society of Gene Therapy\| PubMed ID: 32755566	2020
Outcomes of a Foldable Capsular Vitreous Body Implantation: A Retrospective Study. Disease markers\| PubMed ID: 34987675	2021
Hypoxia-induced AFAP1L1 regulates pathological neovascularization via the YAP-DLL4-NOTCH axis. Journal of translational medicine\| PubMed ID: 37737201	2023
The role of pericyte in ocular vascular diseases. Journal of biomedical research\| PubMed ID: 38808554	2024
Modified protocol for pterygium surgery without blades and electrocoagulation. Frontiers in medicine\| PubMed ID: 40061380	2025

Huimin Ge

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