Reduced Sensitivity To Light Suppression Of Nocturnal Plasma Melatonin In Glaucoma Patients

Abstract

Abstract: : Purpose: The nocturnal secretion of melatonin by the pineal gland is acutely suppressed by light exposure. Intrinsically light sensitive melanopsin containing ganglion cells have been shown to mediate responses to light in the circadian system of rodents. These melanopsin ganglion cells also receive photic inputs from rods and cones. Melanopsin containing ganglion cells have also been shown in humans (Provencio et al., J. Neurosci, 2000; Cooper et al., ARVO 2003). Since a significant degree of ganglion cell loss occurs in severe open angle glaucoma, we investigated whether this ocular disease leads to a reduction of sensitivity to light in glaucoma patients compared to normal subjects. Methods: We assessed the effect of monochromatic light (480 nm) exposure on melatonin secretion at five levels of irradiance (1011–1014 photons/cm2/sec) in healthy subjects and in glaucoma patients (age ranges from 28–40 years). Plasma melatonin levels were measured using a RIA assay in samples collected before, during, and after 1–h nocturnal light stimulation. Melatonin suppression was calculated by comparing the area under the curve of plasma melatonin values during the light stimulation with values at the same time during dark control sessions. Results: The levels of plasma melatonin secretion during in the dark control condition over the entire night–time period (20:00 hrs – 4:00 hrs) as well as prior to light exposure (20:00 hrs – 0:30 hrs) during the test phases was equivalent in both groups. Following monochromatic light exposure, melatonin suppression by light is reduced in glaucoma patients compared to normal subjects. The greatest loss in sensitivity is observed at the lower irradiance levels. Conclusions:The results indicate that glaucoma patients show a reduction in light sensitivity associated with ganglion cell loss. This suggests that ganglion cell loss affects not only ganglion cells which project to the lateral geniculate nucleus, but also retino–hypothalamic projecting melanopsin ganglion cells. This study supports an anatomical reduction of retinal afferents to the suprachiasmatic nucleus previously demonstrated in a rat model of glaucoma (Drouyer et al. ARVO, 2003).

Keywords: melatonin • circadian rhythms • pathology: human