Zinc and Zinc Chelators Modify Taurine Transport in Rat Retinal Cells

AbstractRetinal degenerative disorders, including age-related macular degeneration and retinitis pigmentosa (RP), are characterized by the irreversible loss of photoreceptor cells and retinal pigment epithelial (RPE) cells; however, the long-term effect of implanting both human induced pluripotent stem cell (hiPSC)-derived RPE and photoreceptor for retinal regeneration has not yet been investigated. In this study, we evaluated the long-term effects of hiPSC-derived RPE and photoreceptor cell transplantation in Pde6b knockout rats to study RP; cells were injected into the subretinal space of the right eyes of rats before the appearance of signs of retinal degeneration at 2–3 weeks of age. Ten months after transplantation, we evaluated the cells using fundus photography, optical coherence tomography, and histological evaluation, and no abnormal cell proliferation was observed. A relatively large number of transplanted cells persisted during the first 4 months; subsequently, the number of these cells decreased gradually. Notably, immunohistochemical analysis revealed that the hiPSC-derived retinal cells showed characteristics of both RPE cells and photoreceptors of human origin after transplantation. Functional analysis of vision by scotopic electroretinogram revealed significant preservation of vision after transplantation. Our study suggests that the transplantation of hiPSC-derived retinal cells, including RPE cells and photoreceptors, has a potential therapeutic effect against irreversible retinal degenerative diseases.

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Carbon Dot Nanoparticles: Exploring the Potential Use for Gene Delivery in Ophthalmic Diseases

Nanomaterials ◽

10.3390/nano11040935 ◽

2021 ◽

Vol 11 (4) ◽

pp. 935

Author(s):

Manas R. Biswal ◽

Sofia Bhatia

Keyword(s):

Gene Delivery ◽

Therapeutic Option ◽

Retinal Dystrophy ◽

Retinal Cells ◽

Adeno Associated Virus ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies ◽

Efficient Gene ◽

New Type ◽

Viral Nanoparticles

Ocular gene therapy offers significant potential for preventing retinal dystrophy in patients with inherited retinal dystrophies (IRD). Adeno-associated virus (AAV) based gene transfer is the most common and successful gene delivery approach to the eye. These days, many studies are using non-viral nanoparticles (NPs) as an alternative therapeutic option because of their unique properties and biocompatibility. Here, we discuss the potential of carbon dots (CDs), a new type of nanocarrier for gene delivery to the retinal cells. The unique physicochemical properties of CDs (such as optical, electronic, and catalytic) make them suitable for biosensing, imaging, drug, and gene delivery applications. Efficient gene delivery to the retinal cells using CDs depends on various factors, such as photoluminescence, quantum yield, biocompatibility, size, and shape. In this review, we focused on different approaches used to synthesize CDs, classify CDs, various pathways for the intake of gene-loaded carbon nanoparticles inside the cell, and multiple studies that worked on transferring nucleic acid in the eye using CDs.

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Human primary retinal cells as an in-vitro model for investigating defective signalling caused by OPTN mutants associated with glaucoma

Neurochemistry International ◽

10.1016/j.neuint.2021.105075 ◽

2021 ◽

pp. 105075

Author(s):

Zuberwasim Sayyad ◽

Sushma Vishwakarma ◽

Tarjani Vivek Dave ◽

Milind N. Naik ◽

Vegesna Radha ◽

...

Keyword(s):

In Vitro Model ◽

Retinal Cells ◽

Vitro Model

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Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence

Life ◽

10.3390/life11060591 ◽

2021 ◽

Vol 11 (6) ◽

pp. 591

Author(s):

Toshihiko Matsuo ◽

Shihui Liu ◽

Tetsuya Uchida ◽

Satomi Onoue ◽

Shinsaku Nakagawa ◽

...

Keyword(s):

Biological Evaluation ◽

Pharmacokinetic Studies ◽

Retinal Neurons ◽

Retinal Cells ◽

Intravitreous Injection ◽

Rcs Rats ◽

Photoelectric Dye ◽

Dark Conditions

NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa.

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