Paul David Blakeley

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ophbpd@nus.edu.sg


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OPHTHALMOLOGY
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2020 - 20222
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    A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema
    (MDPI, 2020-09-01) Chan, Hwei Wuen; Yang, Binxia; Wong, Wendy; Blakeley, Paul; Seah, Ivan; Tan, Queenie Shu Woon; Wang, Haofei; Bhargava, Mayuri; Lin, Hazel Anne; Chai, Charmaine HC; Mangunkusumo, Erlangga Ariadarma; Thet, Naing; Yuen, Yew Sen; Sethi, Raman; Wang, Si; Hunziker, Walter; Lingam, Gopal; Su, Xinyi; Dr Hwei Wuen Chan; DUKE-NUS MEDICAL SCHOOL; OPHTHALMOLOGY
    (1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species (N = 315), followed by serum (N = 309), then aqueous humor (N = 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers.
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    Publication
    A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway.
    (Springer Science and Business Media LLC, 2022-05-19) Parikh, Bhav Harshad; Liu, Zengping; Blakeley, Paul; Lin, Qianyu; Singh, Malay; Ong, Jun Yi; Ho, Kim Han; Lai, Joel Weijia; Bogireddi, Hanumakumar; Tran, Kim Chi; Lim, Jason YC; Xue, Kun; Al-Mubaarak, Abdurrahmaan; Yang, Binxia; R, Sowmiya; Regha, Kakkad; Wong, Daniel Soo Lin; Tan, Queenie Shu Woon; Zhang, Zhongxing; Jeyasekharan, Anand D; Barathi, Veluchamy Amutha; Yu, Weimiao; Cheong, Kang Hao; Blenkinsop, Timothy A; Hunziker, Walter; Lingam, Gopal; Loh, Xian Jun; Su, Xinyi; Dr Zengping Liu; MEDICINE; MATERIALS SCIENCE AND ENGINEERING; DIVISION OF BIOENGINEERING; OPHTHALMOLOGY
    One common cause of vision loss after retinal detachment surgery is the formation of proliferative and contractile fibrocellular membranes. This aberrant wound healing process is mediated by epithelial-mesenchymal transition (EMT) and hyper-proliferation of retinal pigment epithelial (RPE) cells. Current treatment relies primarily on surgical removal of these membranes. Here, we demonstrate that a bio-functional polymer by itself is able to prevent retinal scarring in an experimental rabbit model of proliferative vitreoretinopathy. This is mediated primarily via clathrin-dependent internalisation of polymeric micelles, downstream suppression of canonical EMT transcription factors, reduction of RPE cell hyper-proliferation and migration. Nuclear factor erythroid 2-related factor 2 signalling pathway was identified in a genome-wide transcriptomic profiling as a key sensor and effector. This study highlights the potential of using synthetic bio-functional polymer to modulate RPE cellular behaviour and offers a potential therapy for retinal scarring prevention.