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More than 3 decades ago, it was predicted that a laser instrument capable of emitting nanosecond pulses of green light would “activate” irradiated cells due to thermal effects induced by the photothermolysis of melanin granules.1 Only a decade later, the neodymium-doped yttrium aluminum garnet (Nd-YAG) laser instrument became available, as well as the selective laser trabeculoplasty (SLT) procedure.2 Soon thereafter, it was shown that melanin granules in SLT-irradiated TMEs do become depigmented as they undergo “selective” photothermolysis.3,4 Later, it was also learned that SLT-irradiated trabecular meshwork cells (TMEs) and Schlemm's canal endothelial cells (SCEs) undergo the upregulation of numerous genes at the genomic-wide level as they become activated.5–7 On learning that Argon laser-irradiated TMEs secrete IL-1α, IL-1β, and TNF-α,8 we established that SLT-irradiated TMEs and SCEs also secrete the same three cytokines.5,6 Moreover, we also learned that adding selected recombinant cytokines onto SCE monolayers induced marked increases in fluid flow.5,6 Cytokines have also been identified in the aqueous humor of glaucoma patients,9 and certain chemokines are constitutively secreted by TMEs and may maintain a population of resident mononuclear-cells in the conventional aqueous outflow pathway (CAOP).10 Moving forward, using Affymetrix microarrays, we have now identified 28 upregulated and 18 downregulated cytokine genes after exposing TMEs and SCEs to either SLT irradiation or to media conditioned by SLT-irradiated TMEs or SCEs. In addition, we identified six cytokine-receptor genes upregulated or downregulated in TMEs or SCEs after at least one of these treatments. Further, using ELISA and protein antibody arrays, we profiled at least eight upregulated cytokines in SLT-irradiated CAOP explants ex vivo representing an extensive cytokine-driven signaling pathway.