Subretinal Implantation of RPE on a Carrier in Minipigs: Guidelines for Preoperative Preparations, Surgical Techniques, and Postoperative Care.

Degenerative disorders of the retina (including age-related macular degeneration), which originate primarily at or within the retinal pigmented epithelial (RPE) layer, lead to a progressive disorganization of the retinal anatomy and the deterioration of visual function. The substitution of damaged RPE cells (RPEs) with in vitro cultured RPE cells using a subretinal cell carrier has shown potential for re-establishing the anatomical structure of the outer retinal layers and is, therefore, being further studied. Here, we present the principles of a surgical technique that allows for the effective subretinal transplantation of a cell carrier with cultivated RPEs into minipigs.

Mitochondrial Dysfunction in a High Intraocular Pressure-Induced Retinal Ischemia Minipig Model.

Retinal ischemia (RI) and progressive neuronal death are sight-threatening conditions. Mitochondrial (mt) dysfunction and fusion/fission processes have been suggested to play a role in the pathophysiology of RI. This study focuses on changes in the mt parameters of the neuroretina, retinal pigment epithelium (RPE) and choroid in a porcine high intraocular pressure (IOP)-induced RI minipig model.

Subretinal Implantation of Human Primary RPE Cells Cultured on Nanofibrous Membranes in Minipigs.

Purpose: The development of primary human retinal pigmented epithelium (hRPE) for clinical transplantation purposes on biodegradable scaffolds is indispensable. We hereby report the results of the subretinal implantation of hRPE cells on nanofibrous membranes in minipigs.

Methods: The hRPEs were collected from human cadaver donor eyes and cultivated on ultrathin nanofibrous carriers prepared via the electrospinning of poly(L-lactide-co-DL-lactide) (PDLLA).

Advantages of nanofibrous membranes for culturing of primary RPE cells compared to commercial scaffolds.

Purpose: Dysfunction of the retinal pigment epithelium (RPE) causes numerous forms of retinal degeneration. RPE replacement is a modern option to save vision. We aimed to test the results of transplanting cultured RPEs on biocompatible membranes.

Quantitative analysis of the anti-proliferative activity of combinations of selected iron-chelating agents and clinically used anti-neoplastic drugs.

Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and established chemotherapeutics are lacking.

Catalytic inhibitors of topoisomerase II differently modulate the toxicity of anthracyclines in cardiac and cancer cells.

Anthracyclines (such as doxorubicin or daunorubicin) are among the most effective anticancer drugs, but their usefulness is hampered by the risk of irreversible cardiotoxicity. Dexrazoxane (ICRF-187) is the only clinically approved cardioprotective agent against anthracycline cardiotoxicity. Its activity has traditionally been attributed to the iron-chelating effects of its metabolite with subsequent protection from oxidative stress.

Synthesis and biological activity of desmethoxy analogues of coruscanone A.

A series of simple desmethoxy analogues of coruscanone A was prepared via a novel version of Ti(iPrO)(4)-mediated Knoevenagel condensation of cyclopentenedione with substituted benzaldehydes and cinnamic aldehydes, and the compounds were evaluated for antifungal activity and cytotoxicity. The most potent 2-benzylidenecyclopent-4-ene-1,3-dione possessed antifungal effect comparable to coruscanone A and a somewhat broader spectrum of activity against Candida species. The compound was also superior to fluconazole against several non-albicans Candida sp.

3,5-disubstituted pyranone analogues of highly antifungally active furanones: conversion of biological effect from antifungal to cytostatic.

A series of 3-aryl-5-acyloxymethyl-5,6-dihydro-2H-pyran-2-ones, related to highly antifungally active butenolides, was synthesized via cyclization of substituted δ-hydroxy acids as the key step, and evaluated for their in vitro antifungal activity and cytostatic activity. While the extension of the furanone ring to pyranone led to a complete loss of the antifungal effect, some of the compounds displayed promising effect against several cell lines, including the resistant colorectal carcinoma cells.

Antifungal 3,5-disubstituted furanones: From 5-acyloxymethyl to 5-alkylidene derivatives.

5-Acetoxymethyl-3-(4-bromophenyl)-2,5-dihydrofuran-2-one previously described as highly antifungally active was found to provide the corresponding 5-methylene derivative via an unusual DMSO-promoted elimination of the ester group at C5 under antifungal assay conditions. Since the latter possessed nearly the same antifungal effect as that originally reported for the former, the 5-acetoxymethyl furanone just served as a precursor of the actual antifungally active species. A few series of compounds with alkyloxy, aryloxy and alkylidene substituents at C5 of the parent furanone structure were therefore prepared and evaluated.