Mesenchymal Stem Cells With Pharmacological Combinations Necessary to Maximize Retinal Photoreceptor, Outer and Inner Nuclear Layers Rescue.

The rising prevalence of retinal diseases underscores the need for personalized neuroprotection strategies. Mesenchymal stem cells (MSCs) exhibit paracrine neuroprotective potential and are used clinically when transplantation is unnecessary. This study evaluated MSC-mediated photoreceptor rescue and its enhancement using clinically relevant drugs; nicotinamide (NIC), vasoactive intestinal peptide (VIP), retinoic acid (ATRA), or their combination. Optimizing and personalizing treatments in accordance to retinal damage severity maximizes photoreceptor rescue, offering a targeted approach to retinal disease management. Adipose-derived MSCs were cocultured with spontaneously degenerating neuroretina explants for 6 days. VIP (5 µM), NIC (10 mM), and ATRA (5 µM) were applied individually and in combination. Photoreceptor recovery and structural changes in the inner limiting membrane (ILM), outer nuclear layer (ONL), and inner nuclear layer (INL) were assessed using Toluidine, Rhodopsin immunofluorescence, and DAPI staining. MSCs alone improved photoreceptor, ILM, ONL, and INL recovery compared to the control. However, combining VIP, NIC, and ATRA led to greater improvement, with NIC being the most effective single treatment. The combination of VIP and NIC preserved retinal structure better than VIP, NIC, and ATRA together, although none fully restored the original structure. Personalized treatment approaches, combining MSCs with specific drugs, can significantly enhance retinal neuroprotection tailored to the degree of damage, emphasizing the need for individualized strategies in retinal disease management.