Melanin can deplete immunosuppressive substances from the aqueous humor

Heavily pigmented eyes tend to experience greater inflammation than lightly pigmented eyes following trauma and surgery. The purpose of these studies was to test the possibilities that: (i) melanin augments T cell-responses by depleting or neutralizing anti-inflammatory substances that are normally present in the aqueous humor, and (ii) melanin augments extraocular T cell-mediated inflammatory responses. Two types of experiments were performed. First, the capacity of melanin-adsorbed and non-adsorbed rabbit aqueous humor to inhibit the proliferative response of the T cell line D10.G4.1 to IL-1 was tested. Non-adsorbed aqueous humor inhibited T cell proliferation to the background level in unstimulated cultures, whereas melanin-adsorbed aqueous humor enhanced the proliferation of stimulated, but not resting T cells. Next, mice were sensitized to the antigen conalbumin, and challenged in the ear pinna with conalbumin alone, conalbumin + melanin, or melanin alone and delayed-type hypersensitivity (DTH) was measured. Challenge with melanin alone caused some ear swelling, and melanin increased the DTH response to conalbumin. Our findings are consistent with the notion that melanin can augment intraocular inflammation by depleting or neutralizing the inhibitory components of normal aqueous humor, possibly exposing stimulatory components that are normally masked.