Blood-retina barrier permeability is independent of trace substance lipid solubility in retinitis pigmentosa and in the healthy eye

Differential ocular spectrofluorometry was used to assess the passive permeability of the blood-retina barrier in healthy subjects and in patients with retinitis pigmentosa by determination of the rate of inward leakage of fluorescein and fluorescein glucuronide after intravenous injection of fluorescein. In five healthy subjects we found permeabilities of 1.3 (0.6-2.8) nm/s [log-mean (range)] for fluorescein and 1.3 (0.6-3.1) nm/s for fluorescein glucuronide. Six patients with retinitis pigmentosa all had a markedly increased blood-retina barrier leakage, with inward permeabilities of 8.2 (3.4-25) nm/s for fluorescein and 8.2 (5.6-27) nm/s for fluorescein glucuronide. Since no detectable difference was found between the permeabilities of the two tracers the passive permeability of the blood-retina barrier appears to be independent of the 18-fold difference in lipid solubility between the two tracers, both in retinitis pigmentosa and in healthy subjects. Presumably, the structural substrate for leakage of small hydrophilic molecules through the blood-retina barrier is a water-filled pore, since diffusion through lipid cellular membranes would favor fluorescein over its more water soluble glucuronide.