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Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Corneal Dystrophies

Corneal dystrophies include a diverse group of bilateral, hereditary, non-infectious disorders of the cornea, which are confined to the corneal tissue. At Protheragen, we provide complete diagnostics and therapeutics development services for corneal dystrophies.

Overview of Corneal Dystrophies

Corneal dystrophies describe a wide array of inherited disorders that are characterized by progressive corneal opacification and possibly blindness. The bilateral, non-inflammatory, and non-systemic features of these disorders affect different layers of the cornea. Symptoms of corneal dystrophies are associated with clinical presentation, which ranges from mild visual disturbances to severe loss of vision. Based on the primary anatomical location of the abnormalities, corneal dystrophies are classified into anterior, stromal, and posterior corneal dystrophies.

Histopathological analysis of macular corneal dystrophy (MCD).

Fig. 1 Histopathologic features of macular corneal dystrophy (MCD). (Singh S., et al., 2021)

Pathogenesis of Corneal Dystrophies

Corneal dystrophies are caused mainly by genetics and gene mutations which result in the production of abnormal proteins requited by the cornea's tissues.

Meesmann Dystrophy occurs due to abnormal production of keratin in the cornel epithelium as a result of mutation in either the KRT3 or KRT12 gene.
Mutations in the TGFBI gene are responsible for both Granular corneal dystrophy and Reis-Bücklers corneal dystrophy due to the accumulation of the mutant form of transforming growth factor beta induced protein in the corneal stroma.
Macular corneal dystrophy occurs due to the mutation within the CHST6 gene which results to the accumulation of glycosaminoglycans (GAGs) in keratocytes and in the corneal endothelium.
Fuchs Endothelial Corneal Dystrophy (FECD) is known to frequently involve mutation in COL8A2 or TCF4 genes and it affects the endothelial layer of the cornea as well as Descemet's membrane.

Therapeutics Development for Corneal Dystrophies

Gene Therapy
Gene therapy entails the insertion of operational genes to either replace or augment the non-functional genes. It includes gene supplementation, wherein a functioning version of the gene is added, and gene silencing, which employs siRNA or antisense RNA to block the expression of the aberrant gene. Moreover, gene editing aims to exploiting CRISPR/Cas9 technologies to change the genetic sequence that harbors the mutation.
Pharmacological Therapeutics
The use of pharmacological therapeutics encompasses symptom management and inhibition of disease progression which includes the use of medications, topical therapies, gels, ointments, and even therapeutic contact lenses. In the case of epithelial recurrent erosion dystrophy, a combination of antibiotics, cycloplegics, and hypertonic saline are systematically administered to heal epithelial defects while safeguarding the epithelium that is only weakly attached.

Table 1. Corneal in vivo gene therapy. (Salman M., et al., 2022)

PMID Ref	Gene	GT Vector and Delivery Method	Animal Model	Outcome
8641831	lacZ	Reporter genes AV vector [Microinjection to anterior chamber]	Rabbits	Detected endothelial expression after 48h of administration, with a significant sign of inflammation
11895005	GFP	HIV-1-based lentiviral vector [Intracameral injection]	Mice	Led endothelial GFP expression for 12 weeks
11726636	GFP	Baculovirus vector [Intravitreal injection]	Mice	Detected continuous endothelial expression for 14 days after administration.
24607662	GFP	CAV-2 vector [Microinjection]	Mice Gray	Widespread expression in cornea diffused throughout stromal region for a week.
9878215	LacZ	rAV-5 vector [Topical administration]	mouse Lemurs Cotton rats	β-Gal expression was observed in conjunctival epithelium only at 24 and 48 hours.
11867594		White rabbits		Endothelial LacZ expression lasted for 15 days with induction of inflammation
19023450	GFP	rAV and rAAV [Topical administration]	Rabbits	Significant GFP keratocyte expression was detected using AAV, while higher expression IN the cornea was detected using rAV
11950229	LacZ	Plasmid DNA [Electric pulse]	Brown Norway rat	Transgene expression was observed in corneal stroma for 15 days, and was maximum between days 4-6 without apparent ocular damage
15196630	Luciferase	Cationic lipoplexes vector [Intravitreal injection]	Rabbits	Led continuous expression for 1 –7 days, with peak expression at day 3, with maximum expression in aqueous humor
19879644	GFP	NOVAFECT chitosan's oligomer [Intrastromal injection]	Rat	GFP expression was observed in keratocytes after transfection.
20599959	AP	AAV6, AAV8 and AAV9 vector [Topical administration]	Mouse	A continued transgene expression for 30 days was observed without significant apoptotic effect, with maximum transduction efficiency using AAV9
11440623	sFlt-1	rAV vector [Anterior chamber injection]	Rat	Efficient transduction to corneal endothelial cells and trabecular meshwork cells was obtained and maintained for 10 days post-injection.
29259248	HLA-G	AAV vector [Intrastromal injection]	Rabbit	Prevented corneal vascularization, lymphocyte infiltration, and reduced myofibroblast formation significantly.
29875240	Lyir-targeting hammerhead ribozyme	AAV vector [Topical administration to abraded cornea]	Rabbits	AAV vectors expressing LAT-targeting ribozymes prevented the reactivation of the HSV latent infection
7558713	HO-1	Plasmid mixed with lipofectamine [Microinjection to anterior chamber, vitreous cavity, and subretinal space]	Rabbits	Intracameral administration led to both endothelial and epithelial expression, while only endothelial expression was observed when administered by intravitreal injection.

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

At Protheragen, we understand that every client's needs are unique. Therefore, we offer customized services tailored to meet the specific requirements of each project. Whether it's the development of a novel diagnostic test or the preclinical evaluation of a therapeutic candidate, our team will work closely with you to ensure the successful completion of your project.

Diagnostics Development

Therapeutic Development

Disease Models

TCF4 Knockout Mouse Models
SLC4A11 Knockout Mouse Models
TGFBI Gene Editing Models
Chemical Injury Models

Protheragen is at the forefront of corneal dystrophies diagnostics and therapeutics development, offering a comprehensive suite of services that leverage cutting-edge technology and scientific expertise. If you are interested in our services, please feel free to contact us.

References

Singh, Shalini, et al. "Macular corneal dystrophy: an updated review." Current Eye Research 46.6 (2021): 765-770.
Salman, Mohd, et al. "New frontier in the management of corneal dystrophies: basics, development, and challenges in corneal gene therapy and gene editing." The Asia-Pacific Journal of Ophthalmology 11.4 (2022): 346-359.