Noninvasive Monitoring of Choroid-Retina Autofluorescence and Intravitreal Nanoparticle Disposition in Royal College of Surgeon Rats of Different Ages and Retinal Thinning

J Ocul Pharmacol Ther. Jul/Aug 2020;36(6):458-466. doi: 10.1089/jop.2020.0028. Epub 2020 Jun 18.

Abstract

Purpose: To determine the baseline choroid-retina fluorescence signal in Royal College of Surgeon (RCS) rats of various ages with different degrees of retinal degeneration and assess the persistence of intravitreal nanoparticles. Methods: In RCS rats of age 6, 12, and 20 weeks and Sprague Dawley (SD) rats of age 6 and 20 weeks, baseline eye tissue fluorescence and retinal thickness were recorded noninvasively using fluorophotometry and optical coherence tomography (OCT), respectively. Further, 20-nm carboxylate-modified fluorescent particles were injected intravitreally in the above groups of rats, and the depth-wise fluorescence signal was monitored over 7 days using fluorophotometry and confocal laser scanning ophthalmoscopy (cSLO). Additionally, 200 nm particles of the same material were injected intravitreally into about 7-week-old RCS rats and the fluorescence signal was monitored up to 35 days using fluorophotometry. Results: Reduction in retinal thickness and an increase in choroid-retina and lens baseline fluorescence was observed with increasing age of RCS and SD rats. The 20 nm particles persisted in the vitreous of animals from all age groups for at least 7 days postadministration, irrespective of the differences in retinal thickness. cSLO confirmed nanoparticle persistence in the eye. The fluorescence signal from 200 nm particles persisted for 35 days in the vitreous humor. Conclusions: Choroid-retina and lens autofluorescence monitored using fluorophotometry increase with age. Intravitreally injected nanoparticles can be monitored noninvasively in rats using fluorophotometry and cSLO imaging. Both 20 and 200 nm particles persist in the back of the eye tissues, for several days following intravitreal injection.

Keywords: fluorophotometry; intravitreal delivery; nanoparticles; noninvasive monitoring; ocular drug delivery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Choroid / diagnostic imaging
  • Choroid / drug effects
  • Choroid / metabolism*
  • Drug Delivery Systems / methods
  • Drug Monitoring / methods
  • Female
  • Fluorophotometry / methods
  • Intravitreal Injections
  • Male
  • Microscopy, Confocal / methods
  • Models, Animal
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / diagnostic imaging
  • Retina / drug effects
  • Retina / metabolism*
  • Retinal Degeneration / drug therapy*
  • Surgeons / organization & administration
  • Tomography, Optical Coherence / methods
  • Vitreous Body / metabolism