To investigate the microRNA (miRNA) profile in patients with different stages of pseudoexfoliation (PXF). Methods: Peripheral blood of patients with PXF (naïve to medical therapy and with no systemic disease/drugs) with ocular hypertension (OHT) and pseudoexfoliation glaucoma (PXG) was evaluated in triplicate for miRNA profiling using polymerase chain reaction (PCR) arrays. Those identified in the discovery stage were validated with evaluation of serum transforming growth factor-β1 (TGF-β1) levels by ELISA. The downstream targets of TGF-β1 and unfolded protein response (UPR) were analyzed using reverse transcriptionquantitative polymerase chain reaction (RT-qPCR). Predicted targets of the identified miRNA and KEGG pathway analysis were done using miRbase and DIANA tools mirPathv3.1. Results: We found hsa-miR-122-5p, hsa-miR-124-3p and hsa-miR-424-5p to be upregulated in PXG targeting 3 specific pathways namely TGF-β1, fibrosis/ECM and proteoglycan metabolism with common effectors like SMAD/3/2. The unfolded protein response (UPR) genes were significantly downregulated in all stages of PXF suggesting this as the key mechanism for protein aggregates in PXF syndrome. Serum TGF-β1 was significantly upregulated as disease progressed to later stages in PXG. This elevation in advanced stages was associated with significantly differential expression of downstream pathways and fibrotic genes in OHT compared to PXG predominantly through the SMAD3, a canonical pathway marker. Conclusion: Circulatory miRNA differentially regulating TGF-β1 and downstream targets including UPR genes may be the key mechanisms for glaucoma onset in PXF.
PurposeTo evaluate different clinical variants of pseudoexfoliation syndrome and their risk of developing ocular hypertension (OHT) or glaucoma (PXG)DesignCross sectional hospital based study.SettingAll patients seen at glaucoma services of a tertiary eye care center in east India.MethodsElectronic medical records search of hospital database including consecutive new and old cases seen during April 2013 to March 2015 was done to retrieve case sensitive words including pseudoexfoliation, PXF, PEX, PXG and pseudoexfoliative glaucoma over any part of the clinical electronic sheet of the patient. All demographic and clinical details including laterality, the pattern of deposits, need for medicines and disc damage at presentation was compared in eyes with radial pigmentary, classical or combined forms of PXF phenotypes.ResultsOf 110313 PXF patients seen during the period of 2013–2015, a total of 2297 eyes of 1150 PXF patients were identified including 525 unilateral PXF (meaning a total of 1775 PXF eyes with 625 patients having bilateral disease, n = 1250 eyes, other clinically normal eye, n = 522) at presentation. Of 525 unilateral PXF eyes, 105 had OHT and 131 had glaucoma while bilateral cases had more >50% (675 eyes of 1250 eyes) with glaucoma. Glaucoma with significant changes in IOP with or without disc damage was seen in 32% of pigmentary and 39% of classical PXF forms with eyes with combined forms of PXF having around 50% with glaucoma at presentation compared to other forms, p<0.001.ConclusionDifferent phenotypic variants of PXF in this Indian cohort was associated with 30–50% risk of OHT or glaucoma respectively. Adequate care is required while examining the pattern of PXF in each case to prognosticate each patient/eye.
To analyse the disease burden of pseudoexfoliation (PXF) disease stages from East and South India.
DesignProspective hospital based study of patients seen at 4 tertiary centres.
Subjects, participants, and/or controlsConsecutive old and new patients of pseudoexfoliation with normal intraocular pressure (IOP), raised IOP (PXF with Ocular hypertension, OHT) and irreversible disc/field changes (pseudoexfoliation glaucoma, PXG) seen from April 2016-March 2017 at a tertiary centre in Odisha, East India and 3 centres in Andhra Pradesh and Telangana, South India, recruited into the prospective study were screened for baseline characteristics.
MethodsThe clinical and demographic details including visual acuity, laterality, intraocular pressure (IOP) with details of medical/surgical therapy at presentation were collected from the hospital database at all 4 centres.
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