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Nevertheless, due to the ocular barriers and the tight junctions of the retinal pigment epithelium that allow only one to two per cent of the drug to reach the retinal and vitreous regions, frequent administrations are required to obtain the desired therapeutic effect, which may contribute to systemic side effects and poor patient compliance [108, 127]

Together, they help create an environment of long-term cellular resilience

High metabolite cultivation To assess the effects of elevated extracellular metabolites, complete DMEM (5% FBS) was supplemented with 20 mM of each indicated metabolite as following: glutamine, glutamate plus NHCl (equimolar), L-aspartate plus L-citrulline (equimolar), L-arginine