A lab‐on‐a‐chip model of glaucoma

Nafian, Fatemeh; Azad, Babak Kamali Doust; Yazdani, Shahin; Rasaee, Mohammad Javad; Daftarian, Narsis

doi:10.1002/brb3.1799

Cited by 6 publications

(3 citation statements)

References 57 publications

(97 reference statements)

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Section: Resultsmentioning

confidence: 99%

“…An in vitro neurodegenerative model was established in our previous study to evaluate the response of individual cell populations to EHP. [ 19 ] The model has studied retinal ganglion cells (RGCs) utilizing an EHP loading system previously named the “glaucoma-on-a-chip” (GOC) model [Figure 1]. In the current study, SH-SY5Y cells were seeded into sets of 12-well chips and treated using ATRA-BDNF before the pressure experiment.…”

Section: Methodsmentioning

confidence: 99%

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Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model

Nafian,

Yazdani,

Javad Rasaee

et al. 2024

JOVR

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Purpose: RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model. Methods: We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model. Results: The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ[1]carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico, molecular dynamic simulations of the mRNYK–NTRK2 complex showed more stable and stronger interactions as compared to the RNYK–NTRK2 complex. In vitro, mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318. Conclusion: The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model

Nafian,

Yazdani,

Javad Rasaee

et al. 2024

JOVR

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“…The HP (hydrostatic pressure)applied on RGCs was compared with RGCs subjected to neuroprotective growth factor (BDNF) and an alternative commercialized peptide that targets as an agonist for type 2 neurotrophic tyrosine kinase receptor (NTRK2). [ 79 ] The system consisted of continuous perfusion fields, optimized mixed gas composition, and stabilized temperature and osmolarity parameters with the purpose of replicating the in vivo culture conditions. Glaucoma‐on‐a‐chip provided an optimized glaucomatous condition, when subjected to a physiological microenvironment for proper communication of RGCs.…”

Section: Organ‐on‐chip Models For Degenerative Diseasesmentioning

confidence: 99%

Degenerative disease‐on‐a‐chip: Developing microfluidic models for rapid availability of newer therapies

Jahagirdar

Bangde

Jain

et al. 2021

Biotechnology Journal

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Background: Understanding the pathophysiology of degenerative diseases pertaining to nervous system, ocular region, bone/cartilage, and muscle are still being comprehended, thus delaying the availability of targeted therapies.Purpose and Scope: Newer micro-physiological systems (organ-on-chip technology) involves development of more sophisticated devices, modelling a range of in vitro human tissues and an array of models for diseased conditions. These models expand opportunities for high throughput screening (HTS) of drugs and are likely to be rapid and cost-effective, thus reducing extensive usage of animal models. Conclusion:Through this review article, we aim to present an overview of the degenerative disease models that are presently being developed using microfluidic platforms with the aim of mimicking in vivo tissue physiology and micro-architecture. The manuscript provides an overview of the degenerative disease models and their potential for testing and screening of possible biotherapeutic molecules and drugs. It highlights the perspective of the regulatory bodies with respect to the established-on chip models and thereby enhancing its translational potential.

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Mikrochips für die Glaukomtherapie

Kreyenschulte

2023

Handbuch Digitale Gesundheitswirtschaft

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A lab‐on‐a‐chip model of glaucoma

Cited by 6 publications

References 57 publications

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model

Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model

Degenerative disease‐on‐a‐chip: Developing microfluidic models for rapid availability of newer therapies

Mikrochips für die Glaukomtherapie

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