Beyond Melanin Clearance: Melanocyte–Fibroblast Crosstalk and Stromal Matrix Responses to Pigment-Targeted Laser Exposure

The biological consequences of pigment-targeted laser exposure extend beyond visible melanin reduction. The iris stroma is a multicellular microenvironment containing melanocytes, fibroblasts and other stromal cells, vascular and immune populations, and extracellular matrix (ECM). Human iris co-culture studies demonstrate fibroblast-dependent regulation of melanogenic activity, while tissue immunohistochemistry and cell-resolved atlases identify endogenous matrix-regulatory proteins and distinct stromal cell populations. Historical human histopathology following Nd:YAG iridotomy and argon peripheral iridoplasty further documents procedure-dependent patterns of stromal disruption, pigment-bearing cellular responses, fibroblast-like proliferation, and collagen alteration. These findings cannot be transferred directly to selective anterior stromal melanin modulation because the laser mechanisms, exposure architectures and tissue targets differ. This critical translational review integrates human iris evidence with experimental iris-laser histology and clearly distinguished analogies from dermal fibroblast and trabecular-meshwork research. It examines four analytically distinct domains: melanosome modification, melanocyte viability and function, melanocyte–fibroblast signalling, and ECM organisation and turnover. An evidence-stratified experimental agenda is proposed, combining cell-specific assays, protein- and matrix-level measurements, and longitudinal structural assessment. Separating the visible pigmentary endpoint from the biological state of the residual stroma provides a testable basis for future protocol-specific studies.