Dataset Information

Light-induced Nrf2-/- mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel.

ABSTRACT: Elevated oxidative stress and associated reactive oxygen species (ROS) accumulation are hallmarks in the induction and progression of age-related macular degeneration (AMD). By exposing nuclear factor erythroid 2-related factor (Nrf2) knockout (Nrf2-/-) mice to mild white light, we were able to generate a new dry-AMD like murine model to the study. This animal model developed phenotypes of photoreceptor degeneration, retinal function impairment, ROS accumulation, and inflammation reaction in a relatively shorter time. In the treatment of this animal model we utilized an antioxidative and water soluble nanoparticle known as glycol chitosan coated cerium oxide nanoparticles (GCCNP). The delivery of GCCNP protected retina against progressive retinal oxidative damage. Further combination of GCCNP with alginate-gelatin based injectable hydrogel provided synergistic antioxidant effects and achieved a more rapid recovery of the retinal pigment epithelium and photoreceptor cells. This combined treatment technique has the potential to translate into a clinical intervention for the treatment of AMD.

SUBMITTER: Wang K

PROVIDER: S-EPMC6787253 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Light-induced Nrf2<sup>-/-</sup> mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel.

Wang Kai K Zheng Min M Lester Kaitlyn Lee KL Han Zongchao Z

Scientific reports 20191010 1

Elevated oxidative stress and associated reactive oxygen species (ROS) accumulation are hallmarks in the induction and progression of age-related macular degeneration (AMD). By exposing nuclear factor erythroid 2-related factor (Nrf2) knockout (Nrf2<sup>-/-</sup>) mice to mild white light, we were able to generate a new dry-AMD like murine model to the study. This animal model developed phenotypes of photoreceptor degeneration, retinal function impairment, ROS accumulation, and inflammation reac ...[more]

PMID: 31601909

Similar Datasets

Project description:PurposeTo evaluate the therapeutic potential and safety of intravitreal injections of bone marrow mononuclear fraction (BMMF) containing CD34+ cells in patients with atrophic age-related macular degeneration (AMD).MethodsTen patients with atrophic AMD and best-corrected visual acuity (BCVA) in the worse-seeing eye of ≤20/100 were enrolled in this study. The bone marrow from all patients was aspirated and processed for mononuclear cell separation. A 0.1 mL suspension of BMMF CD34+ cells was injected into the vitreous cavity of the worse-seeing eye. Patients were evaluated at Baseline and 1,3,6,9 and 12 months after injection. Ophthalmic evaluation included BCVA measurement, microperimetry, infrared imaging, fundus autofluorescence and SD-optical coherence tomography at all study visits. Fluorescein angiography was performed at Baseline and at 6 and 12 months after intravitreal therapy.ResultsAll patients completed the 6-month follow-up, and six completed the 12-month follow-up. Prior to the injection, mean BCVA was 1.18 logMAR (20/320-1), ranging from 20/125 to 20/640-2, and improved significantly at every follow-up visit, including the 12-month one, when BCVA was 1.0 logMAR (20/200) (P<0.05). Mean sensitivity threshold also improved significantly at 6, 9 and 12 months after treatment (P<0.05). Considering the area of atrophy identified by fundus autofluorescence, significant mean BCVA and mean sensitivity threshold improvement were observed in patients with the smallest areas of atrophy. Fluorescein angiography did not identify choroidal new vessels or tumor growth.ConclusionThe use of intravitreal BMMF injections in patients with AMD is safe and is associated with significant improvement in BCVA and macular sensitivity threshold. Patients with small areas of atrophy have a better response. The paracrine effect of CD34+ cells may explain the functional improvement observed; however, larger series of patients are necessary to confirm these preliminary findings.

Project description:PurposeLoss of photoreceptors in atrophic age-related macular degeneration results in severe visual impairment, although some peripheral vision is retained. To restore central vision without compromising the residual peripheral field, we developed a wireless photovoltaic retinal implant (PRIMA; Pixium Vision, Paris, France) in which pixels convert images projected from video glasses using near-infrared light into electric current to stimulate the nearby inner retinal neurons.DesignWe carried out a first-in-human clinical trial to test the safety and efficacy of the prosthesis in patients with geographic atrophy (ClinicalTrials.gov identifier, NCT03333954).ParticipantsFive patients with geographic atrophy zone of at least 3 optic disc diameters, no foveal light perception, and best-corrected visual acuity of 20/400 to 20/1000 in the worse-seeing study eye.MethodsThe 2-mm wide, 30-μm thick chip, containing 378 pixels (each 100 μm in diameter), was implanted subretinally in the area of atrophy (absolute scotoma).Main outcome measuresAnatomic outcomes were assessed with fundus photography and OCT for up to 12 months of follow-up. Prosthetic vision was assessed by mapping light perception, bar orientation, letter recognition, and Landolt C acuity.ResultsIn all patients, the prosthesis was implanted successfully under the macula, although in 2 patients, it was implanted in unintended locations: within the choroid and off center by 2 mm. All 5 patients could perceive white-yellow prosthetic visual patterns with adjustable brightness in the previous scotomata. The 3 with optimal placement of the implant demonstrated prosthetic acuity of 20/460 to 20/550, and the patient with the off-center implant demonstrated 20/800 acuity. Residual natural acuity did not decrease after implantation in any patient.ConclusionsImplantation of the PRIMA did not decrease the residual natural acuity, and it restored visual sensitivity in the former scotoma in each of the 5 patients. In 3 patients with the proper placement of the chip, prosthetic visual acuity was only 10% to 30% less than the level expected from the pixel pitch (20/420). Therefore, the use of optical or electronic magnification in the glasses as well as smaller pixels in future implants may improve visual acuity even further.

Dataset Information

Light-induced Nrf2-/- mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel.

Publications

Light-induced Nrf2<sup>-/-</sup> mice as atrophic age-related macular degeneration model and treatment with nanoceria laden injectable hydrogel.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets