Altered Anterior Segment Biometric Parameters in Mice Deficient in SPARC

Ho, Henrietta; Htoon, Hla Myint; Yam, Gary Hin‐Fai; Toh, Li Zhen; Lwin, Nyein Chan; Chu, Shaoyan; Lee, Ying Shi; Wong, Tina; Seet, Li‐Fong

doi:10.1167/iovs.16-20261

Cited by 9 publications

(6 citation statements)

References 39 publications

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“…OCT-among other modalities-has been proposed as a noninvasive alternative to histology providing in vivo imaging capabilities with micrometer scale resolution and in real time. OCT has been applied for imaging the anterior murine eye in models of several ophthalmic diseases including a model of Axenfeld-Rieger malformations of the anterior segment related to PITX2 mutation, 30 a DBA/2J model of glaucoma, 31 a mouse model of glaucoma overexpressing bone morphogenetic protein 2, 32 mouse models of elevated IOP, 33,34 mice deficient in secreted protein acidic and rich in cysteine, 35 and phenotypical investigations of genetic components of corneal and stromal thickness relevant for keratoconus. 36 Even though standard (i.e., non-PS) OCT has obviously proven useful for imaging the anterior segment in preclinical studies, PS-OCT studies of the murine eye have thus far been limited to the posterior eye segment.…”

Section: Introductionmentioning

confidence: 99%

Polarization-sensitive optical coherence tomography imaging of the anterior mouse eye

et al. 2018

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Polarization-sensitive optical coherence tomography (PS-OCT) enables noninvasive, high-resolution imaging of tissue polarization properties. In the anterior segments of human eyes, PS-OCT allows the visualization of birefringent and depolarizing structures. We present the use of PS-OCT for imaging the murine anterior eye. Using a spectral domain PS-OCT setup operating in the 840-nm regime, we performed in vivo volumetric imaging in anesthetized C57BL/6 mice. The polarization properties of murine anterior eye structures largely replicated those known from human PS-OCT imagery, suggesting that the mouse eye may also serve as a model system under polarization contrast. However, dissimilarities were found in the depolarizing structure of the iris which, as we confirmed in postmortem histological sections, were caused by anatomical differences between both species. In addition to the imaging of tissues in the anterior chamber and the iridocorneal angle, we demonstrate longitudinal PS-OCT imaging of the murine anterior segment during mydriasis as well as birefringence imaging of corneal pathology in an aged mouse.

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Section: Introductionmentioning

confidence: 99%

Polarization-sensitive optical coherence tomography imaging of the anterior mouse eye

et al. 2018

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“…From a mechanotransduction perspective, matrix stiffness plays a critical role in wound healing and fibrosis, where stiffer matrix (> 5 kPa) has been shown to encourage fibroblast differentiation and progression 23,[48][49][50] . The current hydrogel fabricated is considered soft (< 3.5 kPa for all samples) thus suitable as a therapeutic delivery platform for wound healing and fibrosis treatment.…”

Section: Resultsmentioning

confidence: 99%

Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery

Chun

Yap

Seet

et al. 2021

Sci Rep

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Small interfering RNA (siRNA) therapy is a promising epigenetic silencing strategy. However, its widespread adoption has been severely impeded by its ineffective delivery into the cellular environment. Here, a biocompatible injectable gelatin-based hydrogel with positive-charge tuned surface charge is presented as an effective platform for siRNA protection and delivery. We demonstrate a two-step synthesis of a gelatin-tyramine (Gtn-Tyr) hydrogel with simultaneous charge tunability and crosslinking ability. We discuss how different physiochemical properties of the hydrogel interact with siSPARC (siRNA for secreted protein, acidic and rich in cysteine), and study the positive-charge tuned gelatin hydrogel as an effective delivery platform for siSPARC in anti-fibrotic treatment. Through in vitro studies using mouse tenon fibroblasts, the positive-charge tuned Gtn-Tyr hydrogel shows sustained siSPARC cellular internalization and effective SPARC silencing with excellent biocompatibility. Similarly, the same hydrogel platform delivering siSPARC in an in vivo assessment employing a rabbit model shows an effective reduction in subconjunctival scarring in post glaucoma filtration surgery, and is non-cytotoxic compared to a commonly used anti-scarring agent, mitomycin-C. Overall, the current siRNA delivery strategy involving the positive-charge tuned gelatin hydrogel shows effective delivery of gene silencing siSPARC for anti-fibrotic treatment. The current charge tunable hydrogel delivery system is simple to fabricate and highly scalable. We believe this delivery platform has strong translational potential for effective siRNA delivery and epigenetic silencing therapy.

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“…A severe myocilin glaucoma mutant, Pro370Leu, co-expresses hevin a protein involved in assembly of extracellular matrix [118]. The myocilin mutation causes intracellular accumulation of hevin and reduces its secretion compromising the production of extracellular matrix [119].…”

Section: Myoc Tm Endoplasmic Reticulummentioning

confidence: 99%

Untitled

2020

WJOVR

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Altered Anterior Segment Biometric Parameters in Mice Deficient in SPARC

Abstract: SPARC-null mice have deeper anterior chamber as well as wider drainage angles compared with WT. Therefore, SPARC plays a key role in influencing the spatial organization of the anterior segment, potentially via modulation of collagen properties, while Hevin is not likely to be involved.

Cited by 9 publications

References 39 publications

Polarization-sensitive optical coherence tomography imaging of the anterior mouse eye

Polarization-sensitive optical coherence tomography imaging of the anterior mouse eye

Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery

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