Biology subjects

Muralidharan, A. R.

Publications and source records attributed to Muralidharan, A. R..

5 recordsLinked to original sources

bioRxiv2024

Interactions between high-intensity light and unrestricted vision in the drive for hyperopia

PURPOSETo evaluate the impact of optical versus illuminance factors and their duration-dependency on lens-induced hyperopia (LIH) in chick eyes. METHODSHyperopia was induced in one eye in chicks (10 groups, n=126) from day 1 (D1) post-hatching until D8 using +10 D lenses with fellow eyes as controls. One group (LIH) served as the control without any interventions. Remaining groups were exposed to 2, 4 or 6 hours of unrestricted vision (UnV), high intensity light (HL), or both (HL +UnV). Ocular axial length (AL), refractive error, and choroidal thickness were measured on days 1, 4, and 8. Inter-ocular difference (IOD = experimental - contralateral eye) {+/-} SEM was used to express outcome measures. RESULTSBy D8, LIH decreased AL (-0.42{+/-}0.03 mm) and produced hyperopic refraction (+3.48{+/-}0.32 D) and choroidal thickening (+85.81{+/-}35.23 {micro}m) in the LIH group (all, P<0.001). Exposure to UnV reduced LIH (i.e., hyperopic refraction, axial shortening, and choroidal thickening) in a duration-dependent manner, whereas HL potentiated the development of LIH in a duration-dependent manner. When combined, UnV overpowered HL, with resultant impact on refraction and AL being close to UnV alone, except after 6 hours, when HL+UnV induced shorter AL compared to UnV alone (P=0.03). CONCLUSIONDaily exposure to HL, UnV, and HL+UnV altered LIH in a duration-dependent manner with UnV and LIH producing competing signals. The signal generated by UnV was generally stronger than HL in combined exposure, yet longer durations of HL affected the drive for emmetropization in eyes with UnV.

developmental biology↗

bioRxiv2022

A duration-dependent interaction between high-intensity light and optical refocus in the drive for myopia control

PURPOSETo evaluate the duration-dependent and synergetic impact of high-intensity light (HL) and optical refocus (RF) on lens-induced myopia (LIM) development in chickens. METHODSMyopia was induced in one eye in chicks (10 groups, n=126) from day 1 post- hatching (D1) until D8 using -10D lenses. Fellow eyes remained uncovered as controls. Nine groups were exposed daily to continuous 2 hours (h), 4h, or 6h of either HL (15,000 lux); RF (removal of -10D lens); or both (HL+RF). One group served as the LIM group without any interventions. Ocular axial length (AL), refractive error, and choroidal thickness were measured on D1, D4, and D8. Outcome measures are expressed as inter-ocular difference (IOD= experimental - control eye) {+/-}SEM. RESULTSBy D8, LIM increased AL (0.36{+/-}0.04 mm), myopic refraction (-9.02{+/-}0.37D), and choroidal thinning (-90.27{+/-}16.44 {micro}m) in the LIM group (all, P<0.001). Compared to the LIM group, exposure to 2h, 4h, or 6h of HL, RF, or HL+RF reduced myopic refraction in a duration-dependent manner, with RF being more effective than HL (P<0.05). Only 6h of HL+RF (not 2h or 4h) prevented LIM and was more effective than RF (P=0.004) or HL (P<0.001) in reducing myopic refraction, and more effective than HL (P<0.001) in reducing axial elongation. CONCLUSIONDaily exposure to 2h, 4h, or 6h of HL, RF, or HL+RF reduced lens-induced myopic refraction in a duration-dependent manner in chickens. Only 6h of HL+RF completely stopped LIM development. The synergetic effect of HL and RF is dependent on the duration of the interventions.

neuroscience↗

bioRxiv2022

The Structural Layers of the Porcine Iris Exhibit Inherently Different Biomechanical Properties

PurposeTo isolate the structural components of the ex vivo porcine iris tissue and to determine their biomechanical properties. MethodsThe porcine stroma and dilator tissues were separated, and their dimensions were assessed using optical coherence tomography (OCT). The stroma underwent flow test (n = 32) to evaluate for permeability using Darcys Law ({Delta}P = 2000 Pa, A = 0.0391 mm2), and both tissues underwent stress relaxation experiments ({varepsilon} = 0.5 with initial ramp of {delta}{varepsilon} = 0.1) to evaluate for their viscoelastic behaviours (n = 28). Viscoelasticity was characterised by the parameters {beta} (half width of the Gaussian distribution), {tau}m(mean relaxation time constant), E0 (instantaneous modulus) and E{infty} (equilibrium modulus). ResultsFor the stroma, the hydraulic permeability was 9.49 {+/-} 3.05 x 10-6 mm2/Pa{middle dot}s, and the viscoelastic parameters were {beta} = 2.50 {+/-} 1.40, and {tau}m = 7.43 {+/-} 4.96 s, with the two moduli calculated to be E0= 14.14 {+/-} 6.44 kPa and E{infty} = 6.08 {+/-} 2.74 kPa. For the dilator tissue, the viscoelastic parameters were {beta} = 2.06 {+/-} 1.33 and {tau}m = 1.28 {+/-} 1.27 s, with the two moduli calculated to be E0 = 9.16 {+/-} 3.03 kPa and E{infty} = 5.54 {+/-} 1.98 kPa. ConclusionWe have established a new protocol to evaluate the biomechanical properties of the structural layers of the iris. Overall, the stroma was permeable and exhibited smaller moduli than those of the dilator muscle. An improved characterisation of iris biomechanics may form the basis to further our understanding of angle closure glaucoma.

bioengineering↗

bioRxiv2022

A combination of Metformin and Epigallocatechin Gallate Potentiates Glioma Chemotherapy in vivo

Glioma is the most devastating high-grade tumor of the central nervous system, with dismal prognosis. Existing treatment modality does not provide substantial benefit to patients and demands novel strategies. One of the first-line treatments for glioma, temozolomide, provides marginal benefit to glioma patients. Repurposing of existing non-cancer drugs to treat oncology patients is gaining momentum in recent years. In this study, we investigated the therapeutic benefits of combining three repurposed drugs, namely, metformin (anti-diabetic) and epigallocatechin gallate (green tea-derived antioxidant) together with temozolomide in a glioma-induced xenograft rat model. Our triple-drug combination therapy significantly inhibited tumor growth in vivo and increased the survival rate (50%) of rats when compared with individual or dual treatments. Molecular and cellular analyses revealed that our triple-drug cocktail treatment inhibited glioma tumor growth in rat model through ROS-mediated inactivation of PI3K/AKT/mTOR pathway, arrest of the cell cycle at G1 phase and induction of molecular mechanisms of caspases-dependent apoptosis. In addition, the docking analysis and quantum mechanics studies performed here hypothesize that the effect of triple-drug combination could have been attributed by their difference in molecular interactions, that maybe due to varying electrostatic potential. Thus, repurposing metformin and epigallocatechin gallate and concurrent administration with temozolomide would serve as a prospective therapy in glioma patients.

cancer biology↗

bioRxiv2021

Recovery from form-deprivation myopia in chicks is dependent upon the fullness and correlated colour temperature of the light spectrum

BackgroundTo evaluate the impact of full-spectrum light-emitting diodes (LEDs) mimicking sunlight on ocular axial elongation and refractive error development in a chicken model of myopia. MethodsA total of 39 chicks (Lohmann brown), 1 day-old, were randomly distributed into 3 groups. Animals were housed for 28 days in a temperature-controlled enclosure, under a 12/12h light/dark cycle of isoluminant ([~]285 Lux) fluorescent [n = 18, (4000K, FL-4000)] or Sunlike-LED [n=12, (4000K, SL-4000); n = 9, (6500K, SL-6500)] white lights. Myopia was induced monocularly in all chicks by random occlusion of one eye with a frosted diffuser, from day 1 post-hatching (D1) until D14. On D14, diffusers were removed, and recovery from myopia was monitored under the same experimental light condition. Axial length (AL), refractive status, choroidal thickness and anterior chamber depth were recorded on days 1, 7, 14, 22 and 28. Ex vivo scleral collagen fibre thicknesses were measured from scanning electron microscopy images. Differences in outcome measures between eyes and groups were compared using 2-way repeated-measures ANOVA. ResultsThere was no significant difference between groups in the AL and refraction of form-deprived (FD) eyes during form-deprivation (D1 to D14). FD eyes of animals raised under SL-4000 and SL-6500 recovered more rapidly from excessive axial elongation than those of animals raised under FL-4000, by D22 and D28. Correspondingly, the refractive status of FD eyes exposed to SL-4000 and SL-6500 was close to that of control eyes by D28. The choroid became thicker during recovery in FD eyes compared to control eyes, in all groups. Choroidal thickness was significantly greater in FD eyes of chickens raised under SL-6500 than in animals raised under FL-4000 (P < 0.01). The diameter of scleral collagen fibrils was significantly greater in recovering FD eyes of chickens raised under SL-6500, than in those raised under FL-4000 (P = 0.04) and SL-4000 (P = 0.002). ConclusionsCompared to fluorescent light, moderate intensities of full-spectrum Sunlike-LEDs can accelerate recovery from form-deprivation myopia in chickens, potentially through choroid-mediated pathways increasing the diameter of scleral collagen fibrils. This study highlights an important implication of the spectral content of white light on ocular growth and emmetropization.

neuroscience↗