Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights.

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence.

Measuring spatial visual loss in rats by retinotopic mapping of the superior colliculus using a novel multi-electrode array technique.

Background: The retinotopic map property of the superior colliculus (SC) is a reliable indicator of visual functional changes in rodents. Electrophysiological mapping of the SC using a single electrode has been employed for measuring visual function in rat and mouse disease models. Single electrode mapping is highly laborious requiring long-term exposure to the SC surface and prolonged anesthetic conditions that can adversely affect the mapping data.

Scaling up polarized RPE cell supernatant production on parylene membrane.

Age-related macular degeneration (AMD), a leading cause of vision loss, primarily arises from the degeneration of retinal pigment epithelium (RPE) and photoreceptors. Current therapeutic options for dry AMD are limited. Encouragingly, cultured RPE cells on parylene-based biomimetic Bruch's membrane demonstrate characteristics akin to the native RPE layer.

Polarized RPE Secretome Preserves Photoreceptors in Retinal Dystrophic RCS Rats.

Retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa, lack effective therapies. Conventional monotherapeutic approaches fail to target the multiple affected pathways in retinal degeneration. However, the retinal pigment epithelium (RPE) secretes several neurotrophic factors addressing diverse cellular pathways, potentially preserving photoreceptors.

Development of a Surgical Technique for Subretinal Implants in Rats.

Retinal degeneration, such as age-related macular degeneration (AMD), is a leading cause of blindness worldwide. A myriad of approaches have been undertaken to develop regenerative medicine-based therapies for AMD, including stem cell-based therapies. Rodents as animal models for retinal degeneration are a foundation for translational research, due to the broad spectrum of strains that develop retinal degeneration diseases at different stages.

An Oral Polyphenol Formulation to Modulate the Ocular Surface Inflammatory Process and to Improve the Symptomatology Associated with Dry Eye Disease.

Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life.

Development of Moderate Intensity Focused Ultrasound (MIFU) for Ocular Drug Delivery.

The purpose of this study is to develop a method for delivering antiinflammatory agents of high molecular weight (e.g., Avastin) into the posterior segment that does not require injections into the eye (i.

Tissue Engineering Strategies for Retina Regeneration.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision.

Blocking Ocular Sympathetic Activity Inhibits Choroidal Neovascularization.

To investigate how modulating ocular sympathetic activity affects progression of choroidal neovascularization (CNV), a hallmark feature of wet age-related macular degeneration (AMD). In the first of two studies, Brown Norway rats underwent laser-induced CNV and were assigned to one of the following groups: daily eye drops of artificial tears ( = 10; control group); daily eye drops of the β-adrenoreceptor agonist isoproterenol ( = 10); daily eye drops of the β-adrenoreceptor antagonist propranolol ( = 10); sympathetic internal carotid nerve (ICN) transection 6 weeks prior to laser-induced CNV ( = 10). In the second study, rats underwent laser-induced CNV followed by ICN transection at different time points: immediately after the laser injury ( = 6), 7 days after the laser injury ( = 6), and sham surgery 7 days after the laser injury ( = 6; control group).

Long-Term Transplant Effects of iPSC-RPE Monolayer in Immunodeficient RCS Rats.

Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In many preclinical studies, RPE cells are transplanted as a cell suspension into immunosuppressed animal eyes and transplant effects have been monitored only short-term. We investigated the long-term effects of human Induced pluripotent stem-cell-derived RPE (iPSC-RPE) transplants in an immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction led to photoreceptor degeneration.

Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats.

End-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effective strategies for treating permanent retinal damages.

Xeno-free cryopreservation of adherent retinal pigmented epithelium yields viable and functional cells in vitro and in vivo.

Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw.

High resolution optical coherence elastography of retina under prosthetic electrode.

Background: Quantitatively investigating the biomechanics of retina with a retinal prosthetic electrode, we explored the effects of the prosthetic electrode on the retina, and further supplemented data for a potential clinical trial.

Methods: Biomechanical properties were assessed with a high resolution optical coherence tomography (OCT) based elastography (OCE) system. A shaker was used to initiate elastic waves and an OCT system was used to track axial displacement along with wave propagation.

In Vivo Experimental and Analytical Studies for Bevacizumab Diffusion Coefficient Measurement in the Rabbit Vitreous Humor.

In order to measure the effective diffusion coefficient of Bevacizumab (Avastin, Genentech) in the vitreous humor, a new technique is developed based on the "contour method" and in vivo optical coherence tomography measurements. After injection of Bevacizumab-fluorescein conjugated compound solution into the rabbit eye, the contours of drug concentration distribution at the subsurface of injection were tracked over time. The 2D contours were extrapolated to 3D contours using reasonable assumptions and a numerically integrated analytical model was developed for the theoretical contours for the irregularly shaped drug distribution in the experimental result.

Sympathetic Effects of Internal Carotid Nerve Manipulation on Choroidal Vascularity and Related Measures.

Purpose: To investigate specific effects of denervation and stimulation of the internal carotid nerve (ICN) on the choroid and retina.

Methods: Female Sprague Dawley rats underwent unilateral ICN transection (n = 20) or acute ICN electrical stimulation (n = 7). Rats in the denervation group were euthanized 6 weeks after nerve transection, and eyes were analyzed for changes in choroidal vascularity (via histomorphometry) or angiogenic growth factors and inflammatory markers (via ELISA).

Stereological Method in Optical Coherence Tomography for In Vivo Evaluation of Laser-Induced Choroidal Neovascularization.

Background And Objective: To evaluate a stereological method in optical coherence tomography (OCT) as an in vivo volume measurement of laser-induced choroidal neovascularization (L-CNV) lesion size.

Patients And Methods: Laser photocoagulation was applied in rats to rupture Bruch's membrane and induce L-CNV. In vivo OCT images of neovascular lesions were acquired with a spectral-domain OCT system at days 0, 3, 7, 10, and 14 after laser surgery.

A new immunodeficient retinal dystrophic rat model for transplantation studies using human-derived cells.

Purpose: To create new immunodeficient Royal College of Surgeons (RCS) rats by introducing the defective MerTK gene into athymic nude rats.

Methods: Female homozygous RCS (RCS-p+/RCS-p+) and male nude rats (Hsd:RH-Foxn1, mutation in the foxn1 gene; no T cells) were crossed to produce heterozygous F1 progeny. Double homozygous F2 progeny obtained by crossing the F1 heterozygotes was identified phenotypically (hair loss) and genotypically (RCS-p+ gene determined by PCR).

One-Year Feasibility Study of Replenish MicroPump for Intravitreal Drug Delivery: A Pilot Study.

Purpose: To determine the feasibility of the surgical procedure and to collect some safety data regarding the bioelectronics of a novel micro drug pump for intravitreal drug delivery in a Beagle dog model for up to 1 year.

Methods: Thirteen Beagle dogs were assigned to two groups. The experimental group ( = 11) underwent pars plana implantation of MicroPump; the body of which was sutured episclerally, while its catheter was secured at a pars plana sclerotomy.

Long-term follow-up of photoreceptor loss and recovery after half-fluence photodynamic therapy for chronic central serous chorioretinopathy.

Purpose: To describe a case of chronic central serous chorioretinopathy with apparent transient, reversible loss of photoreceptor outer segments after half-fluence photodynamic therapy (PDT).

Methods: The authors reviewed the clinical and imaging records over a 2-year period of a case of chronic central serous chorioretinopathy treated with PDT.

Results: A 58-year-old man with a 3-year history of blurry central vision in his right eye due to persistent subretinal fluid associated with central serous chorioretinopathy elected to undergo half-fluence verteporfin PDT.