Uent causes of blindness worldwide with a increasing prevalence (GBaVI, 2021). Chronic hyperglycemia in diabetes sufferers induces the activation of leukocytes in the periphery (Chen et al., 2019) also as micro- and macroglial cells inside the retina (Mizutani et al., 1998; Gerhardinger et al., 2005; Zeng et al., 2008). This results in the release of pro-inflammatory Fibroblast Growth Factor 7 (FGF-7) Proteins supplier cytokines and at some point leads to photoreceptor cell death (Coughlin et al., 2017; Kinuthia et al., 2020). Microglial cells, the resident immune cells with the retina, are acknowledged as the primary drivers of retinal immune responses (Karlstetter et al., 2015). However, growing proof suggests that the interaction of micro- and macroglial cells essentially Integrin alpha-6 Proteins web shapes retinal inflammation and photoreceptor degeneration (Wang et al., 2011; Di Pierdomenico et al., 2020). Retinal M ler glial cells constitute the primary macroglial cells on the retina (Reichenbach and Bringmann, 2020). They span the entire width on the retina and are in close make contact with with all the vitreous, the retinal blood-vessels and with all retinal neurons (Newman and Reichenbach, 1996). When they maintain retinal homeostasis during steady-state circumstances, activation of M ler cells below pathological situations results in gliosis, a cellular try to restore insulted tissue, with both protective and detrimental effects (Bringmann et al., 2006). It can be known that M ler cells are an essential supply of neurotrophic things but in addition of pro-inflammatory and angiogenetic cytokines (Bringmann et al., 2009; Ruzafa et al., 2018; von Toerne et al., 2014; Hauck et al., 2007). They play an essential role in DR pathogenesis (Subirada et al., 2018; Ghaseminejad et al., 2020) and it was also suggested that they are involved in retinal immune responses (Roberge et al., 1988; Rutar et al., 2015; Natoli et al., 2017; Lorenz et al., 2021a; Lorenz et al., 2021b). Nonetheless, the impact of their protective or detrimental effects on retinal inflammation in DR and also other neurodegenerative retinal diseases remains elusive so far. Hence, we performed an indepth-analysis from the M ler cell proteome and secretome just after stimulation with numerous pro- and anti-inflammatory cytokines also as growth elements. For our evaluation, we utilized cells with the human M ler glia cell-line MIO-M1 too as major porcine retinal M ler Glia (pRMG), as porcine eyes resemble human eyes regarding their anatomy (Middleton S. Porcine ophthalmology, 2010). In addition, the pig is established as a helpful model for research in diabetic retinopathy (Kleinwort et al., 2017; Renneret al., 2020). Comparative quantitative proteomic analysis permits to elucidate important proteins or pathways involved in disease pathogenesis. In addition, this strategy enables the discovery of new biomarkers and has as a result established as a valuable tool for deciphering pathophysiological important mechanisms (Konigsberg et al., 2021; Weigand et al., 2021). Our hypothesis-generating study yielded extensive data on the capacity of M ler cells to react in a quite differentiated manner to varying stimulants. Additionally to the secretion of pro-inflammatory cytokines, we observed expression of MHC class I and II molecules and proteins which are connected with all the processing of antigens. We hence propose that M ler cells are crucial modulators of your retinal immune response and could possibly exert an antigenpresenting function. As a result, attention should be paid to their implication in chronic inflammation underlying degene.