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Journal of Controlled Release :... Oct 2022CRISPR/Cas9-based genome-editing therapies are poised to change the clinical outcome for many diseases with validated therapeutic targets awaiting an appropriate...
CRISPR/Cas9-based genome-editing therapies are poised to change the clinical outcome for many diseases with validated therapeutic targets awaiting an appropriate delivery system. Recent advances in lipid nanoparticle (LNP) technology make them an attractive platform for the delivery of various forms of CRISPR/Cas9, including the efficient and transient Cas9/gRNA ribonucleoprotein (RNP) complexes. In this study, we initially tested our novel LNP platform by delivering pre-complexed RNPs and template DNA to cultured mouse cortical neurons, and obtained successful ex vivo genome editing. We then directly injected LNP-packaged RNPs and DNA template into the mouse cornea to evaluate in vivo delivery. For the first time, we demonstrated wide-spread genome editing in the cornea using our LNP-RNPs. The ability of our LNPs to transfect the cornea highlights the potential of our novel delivery platform to be used in CRISPR/Cas9-based genome editing therapies of corneal diseases.
Topics: Animals; CRISPR-Cas Systems; Cornea; DNA; Gene Editing; Liposomes; Mice; Nanoparticles; Ribonucleoproteins; RNA, Guide, CRISPR-Cas Systems
PubMed: 36029893
DOI: 10.1016/j.jconrel.2022.08.042 -
Indian Journal of Ophthalmology Dec 2022Aniridia is a pan-ocular genetic developmental eye disorder characterized by complete or partial iris and foveal hypoplasia, for which there is no treatment currently.... (Review)
Review
Aniridia is a pan-ocular genetic developmental eye disorder characterized by complete or partial iris and foveal hypoplasia, for which there is no treatment currently. Progressive sight loss can arise from cataracts, glaucoma, and aniridia-related keratopathy, which can be managed conservatively or through surgical intervention. The vast majority of patients harbor heterozygous mutations involving the PAX6 gene, which is considered the master transcription factor of early eye development. Over the past decades, several disease models have been investigated to gain a better understanding of the molecular pathophysiology, including several mouse and zebrafish strains and, more recently, human-induced pluripotent stem cells (hiPSCs) derived from aniridia patients. The latter provides a more faithful cellular system to study early human eye development. This review outlines the main aniridia-related animal and cellular models used to study aniridia and highlights the key discoveries that are bringing us closer to a therapy for patients.
Topics: Humans; Animals; Mice; Zebrafish; Aniridia; Iris; Cataract; Glaucoma; PAX6 Transcription Factor
PubMed: 36453299
DOI: 10.4103/ijo.IJO_316_22 -
Experimental Eye Research Mar 2021There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism),... (Review)
Review
There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.
Topics: Autoimmune Diseases; COVID-19; Comorbidity; Cornea; Humans; SARS-CoV-2
PubMed: 33485845
DOI: 10.1016/j.exer.2021.108455 -
European Journal of Human Genetics :... Oct 2012Aniridia is a rare congenital disorder in which there is a variable degree of hypoplasia or the absence of iris tissue associated with multiple other ocular changes,... (Review)
Review
Aniridia is a rare congenital disorder in which there is a variable degree of hypoplasia or the absence of iris tissue associated with multiple other ocular changes, some present from birth and some arising progressively over time. Most cases are associated with dominantly inherited mutations or deletions of the PAX6 gene. This article will review the clinical manifestations, the molecular basis including genotype-phenotype correlations, diagnostic approaches and management of aniridia.
Topics: Aniridia; Eye Proteins; Genotype; Homeodomain Proteins; Humans; Intellectual Disability; Mutation; PAX6 Transcription Factor; Paired Box Transcription Factors; Phenotype; Repressor Proteins; Syndrome; Urogenital Abnormalities; WT1 Proteins; Wilms Tumor
PubMed: 22692063
DOI: 10.1038/ejhg.2012.100 -
Cureus Oct 2022Cataract is the leading cause of childhood blindness in developing countries. Early detection and treatment of childhood cataracts can reduce the burden of blindness in... (Review)
Review
Cataract is the leading cause of childhood blindness in developing countries. Early detection and treatment of childhood cataracts can reduce the burden of blindness in the nation. Often the etiology of pediatric cataract is idiopathic; however, genetics play a role in the development of congenital cataract. According to epidemiologists, one-fourth of cases of congenital cataracts are hereditary. Gene responsible for the development of cataract is identified using gene mapping, which helps to prevent future blindness in the family. Cataracts can also present with systemic disease, microphthalmia, microcornea, and aniridia. The presentation of cataracts varies in individuals, some are symptomatic while others are asymptomatic. Parents after noticing strabismus and leukocoria bring their children to an ophthalmologist. Early diagnosis can restore visual function in cases of congenital cataract. In young babies, the type of cataract is determined using slit-lamp examination and examination under anesthesia in OR. Most cases of pediatric cataracts are accidental findings during routine checkups. On direct ophthalmoscopy, red reflex is not appreciated in cases of cataracts. Advancing technology changes the ophthalmologist's approach to pediatric cataract surgery, improving postoperative refractory function. In children, minor incision surgery was preferred to heal early. An appropriate choice of intraocular lens (IOL) should be made for implantation in a child's eye to avoid postimplanted complications. Inflammation and amblyopia affect the outcome of treatment. Complications of cataract surgery include posterior capsule opacification, glaucoma, inflammation, and uveitis.
PubMed: 36381901
DOI: 10.7759/cureus.30135 -
Acta Ophthalmologica Nov 2008
Topics: Aniridia; Cataract; Cataract Extraction; Corneal Diseases; Glaucoma; Humans; Norway; Prevalence; Sweden; Vision, Low
PubMed: 19032333
DOI: 10.1111/j.1755-3768.2008.01402.x