The adult central nervous system exhibits a limited capacity for neuronal regeneration, with retinal ganglion cells being particularly refractory to repair. Although this limitation is frequently attributed to neuron-intrinsic constraints, the contribution of the extracellular glial environment remains incompletely understood. Here, we describe a Müller glial phenotype derived from large baleen whales that supports retinal ganglion cell survival and neurite extension. Using cross-species co-culture and conditioned-medium approaches, we show that whale Müller glia enhance neuronal viability and neurite elongation compared with Müller glia from pigs and rats. Quantitative proteomic profiling and functional annotation suggested species-dependent differences in conditioned-medium composition. Whale Müller glia-conditioned medium contained a broader repertoire of proteins associated with neuroprotection and neurite growth and a lower representation of proteins linked to inhibitory regulation than pig Müller glia-conditioned medium. Among the identified candidates, mesencephalic astrocyte-derived neurotrophic factor (MANF) showed greater abundance in whale conditioned medium, whereas fibronectin leucine-rich transmembrane protein 2 (FLRT2), a molecule associated with axon repulsion, was detected in pig conditioned medium. Functional perturbation experiments showed that FLRT2 suppression enhanced neurite outgrowth in a subset of cells within the RGC-enriched cultures when combined with MANF, but only in the presence of Müller glia, suggesting a glia-dependent effect. Overall, this study identifies species-associated differences in Müller glia-conditioned media and candidate molecular signals that may contribute to retinal neuronal survival and neurite outgrowth.