Laser Damage to Retinal Ganglion Cells: The Effect On Circadian Rhythms

Bughi S, Shaw S, Bessman A. J Diabetes Complications. 2006;20:184-187.

The circadian clock, regulated by the retinal ganglion cells (RGC), influences many physiological systems. The RGC, which contains the photo pigment melanopsin,  helps move  photic information to the suprachiasmatic nucleus (SCN) and eventually to the pineal gland, which in turn secretes melatonin. Melatonin, one of the most important indicators of the circadian clock, has an influential role on the circadian rhythm. Many patients with diabetic proliferative retinopathy undergo laser therapy (LRx), which may damage the RGC and eventually the entire retinal structure. The purpose of this study was to establish the changes in plasma cortisol levels as an indicator of the circadian clock. These measurements were then used to assess the effect of bilateral laser treatment on the circadian rhythm.

A group of 22 patients with type 2 diabetes was drafted from the inpatient Diabetes Service. Each participant was 10-14 days post-local surgery; at baseline, their surgical site showed complete healing. Inclusion criteria comprised absence of pain, infection, and hypoglycemia. Fasting blood glucose levels ranged between 100-180 mg/dL. Based on each participant’s history of diabetic retinopathy and laser treatment, patients were divided into two groups. The first group consisted of 10 patients with type 2 diabetes without retinopathy and LRx, and the second group included 10 patients with type 2 diabetes with a history of retinopathy and bilateral laser treatment. Plasma cortisol and serum cortisol concentrations were measured through blood samples taken at 0800, 1600, and 2400 hours. The range in which cortisol levels were considered normal varied with respect to the time measurements were taken. Normal 0800 h values were between 4.3 and 22.4 mcg/dL; the values defining normal decreased at 1600 h (3.1-16.7 mcg/dL) and 2400  h (<2.0 mcg/dL).

The circadian rhythm of melatonin release runs parallel to the rhythmic release of CRH, a neuroendocrine factor. The release of CRH results in the 24-hour cycle in which ACTH and cortisol are secreted. In blind individuals who cannot secrete ACTH or cortisol, melatonin assists in normalizing the temporal pattern of cortisol secretion; this results in a steady decrease in cortisol levels during the first half of sleep. However, the study results indicate that patients who underwent bilateral laser treatment for diabetic retinopathy had significantly higher cortisol levels compared with the control group. For instance, although the 0800 h values were not very different in the control group versus the laser-treated group (15.2±5.3 vs 12.4±5.5, P  = .50), the 1600 h plasma cortisol level (6.9±4.0 vs 10.2±2.5, P  = .05) and the 2400 h values (2.6±1.7 vs 6.4±2.5, P  = .01) were significantly higher in the laser treated group. The variation in the results suggests that laser-treated patients may have some degree of retinal damage that consequently alters the normal circadian rhythm of cortisol levels and causes nocturnal hypercortisolemia.