Polymeric Nanoparticles for Drug Delivery to the Posterior Segment of the Eye

Diseases of the posterior segment of the eye account for most cases of irreversible blindness worldwide. Drug delivery to this closed compartment remains a challenge because of the internal and external blood retinal barriers that selectively control drug penetration into the retina. Direct intraocular (intravitreal) delivery is currently used to achieve high drug concentration in the vitreous and the retina but is usually associated with several side effects. Alternatively topical, periocular, and systemic routes of administration can be used but are associated with low bioavailability and specific side effects. Therefore, intraocular sustained drug delivery systems are being designed to overcome these limitations. Polymeric nanoparticles loaded with therapeutic compounds are under investigation to provide new tools of administration to the eye. The first part of this paper will briefly review the barriers to ocular delivery of drugs and the advantages of using polymeric nanoparticle carriers as drug delivery systems. In the second part, the results in terms of preparation and characterization of polymeric nanoparticles loaded with nucleic acids, the study of the transretinal pathway of intravitreally injected nanoparticles and the assessment of their ability to efficiently deliver plasmids and oligonucleotides will be discussed

Clinical and molecular findings in three Lebanese families with Bietti crystalline dystrophy: Report on a novel mutation

Purpose: Bietti crystalline dystrophy (BCD) is a rare autosomal recessive disorder caused by mutation of the cytochrome P450, family 4, subfamily V, polypeptide 2 (CYP4V2) gene and characterized by retinal pigmentary abnormalities and scattered deposits of crystals in the retina and the marginal cornea. The aim of this study was to investigate the spectrum of mutations in CYP4V2 in Lebanese families, and to characterize the phenotype of patients affected with BCD. Methods: Nine patients from three unrelated Lebanese families were clinically and molecularly investigated. Detailed characterization of the patients' phenotype was performed with comprehensive ophthalmic examination, color vision study, fundus photography, visual field testing, retinal fluorescein angiography, electroretinography, and electrooculography. One family was followed for 12 years. The 11 exons of the CYP4V2 gene were sequenced. Results: Symptoms consisting of night blindness, loss of paracentral visual field, and disturbed color vision were apparent during the third decade of life. Ophthalmoscopy revealed posterior pole crystalline deposits and areas of retinal pigment epithelium atrophy. Fluorescein angiography disclosed geographic areas of the pigment epithelium layer and choriocapillaris atrophy in the posterior pole and fundus periphery. The most striking findings were those of normal electroretinographic responses in some patients and clinical heterogeneity. Two mutations in CYP4V2 were found: p.I111