In this study, we chose (+)-pentazocine for S1R modulation for two main reasons: (1) it is well-established as a high-affinity (6.7 nM), high-selectivity S1R ligand (>200 fold over S2R) [6] and (2) it has been repeatedly shown to be photoreceptor-protective in RP and diabetic retinopathy models [21,22,23,24] but has not been tested in an AMD-related model in vivo [16]. This evidence concerns the gene TMBIM4 and diabetic retinopathy.