Glial cell and inflammatory responses to retinal laser treatment: comparison of a conventional photocoagulator and a novel, 3-nanosecond pulse laser

Abstract

PURPOSE: Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. METHODS: Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3-ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm2/pulse) and at supra- and subvisible thresholds for the 2RT laser (“high,” 2RT-H, 163 mJ/cm2/pulse; “low,” 2RT-L, 109 mJ/cm2/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. RESULTS: The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Müller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. CONCLUSIONS: The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.