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Worldwide, 1 in 2000 people suffer from inherited retinal dystrophies (IRD). Individuals with IRD typically present with progressive vision loss that ultimately results in blindness. Unfortunately, effective treatment options are not widely available due to the genetic and clinical heterogeneity of these diseases. There are multiple gene, cell, and drug-based therapies in various phases of clinical trials for IRD. This mini-review documents current progress made in drug-based clinical trials for treating IRD.

Retinitis pigmentosa refers to a large, genetically heterogeneous group of retinal dystrophies. This condition is characterized by the gradual onset of blindness due to progressive deterioration of the retina, a process that includes photoreceptor and retinal-pigmented-epithelium cell decay and death, microglial recruitment, reactive gliosis, and vascular disorganization and regression. We found that early in the degenerative process, the rd10 mouse retina exhibits high levels of photoreceptor cell death and reactive Müller gliosis. In explant cultures, both degenerative processes were abrogated by IGF-I treatment. Moreover, the beneficial effect of IGF-I was diminished by microglial depletion using clodronate-containing liposomes. Interestingly, in the absence of IGF-I, microglial depletion partially prevented cell death without affecting Müller gliosis. These findings strongly suggest a role for microglia-Müller glia crosstalk in neuroprotection. However, a subpopulation of microglial cells appears to promote neurodegeneration in the dystrophic retina. Our findings indicate that beneficial neuroprotective effects may be achieved through strategies that modulate microglial cell responses.

Retinal degenerative disease involving photoreceptor (PR) cell loss results in permanent vision loss and often blindness. Generation of induced pluripotent stem cell (iPSC)-derived retinal cells and tissues from individuals with retinal dystrophies is a relatively new and promising method for studying retinal degeneration mechanisms in vitro. Recent advancements in strategies to differentiate human iPSCs (hiPSCs) into 3D retinal eyecups with a strong resemblance to the mature retina raise the possibility that this system could offer a reliable model for translational drug studies. However, despite the potential benefits, there are challenges that remain to be overcome before stem-cell-derived retinal eyecups can be routinely used to model human retinal diseases. This chapter will discuss both the potential of these 3D eyecup approaches and the nature of some of the challenges that remain.