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Project Description

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.

Diabetic Retinopathy (DR)

Diabetic retinopathy, or DR, is a pertinent complication of diabetes mellitus that threatens vision. Protheragen strives to promote innovation of diabetic retinopathy R&D. With our comprehensive diagnostic and therapeutics development services and preclinical research services, we are positioned in this area.

Overview of Diabetic Retinopathy (DR)

Diabetic retinopathy is divided into two phases: non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). During NPDR, initial microvascular changes take place that include the presence of microaneurysms, retinal hemorrhage, and intraretinal microvascular abnormalities (IRMA). While these changes do not exhibit symptoms, they can cause substantial visual loss if left untreated.

Schematic overview of pathogenic mechanisms leading to the sight-threatening endpoints of DR.

Fig.1 Pathogenic mechanisms leading to vision-threatening endpoints in diabetic retinopathy (DR). (Lechner J., et al., 2017)

The greater stage, PDR, is distinguished by neovascularization and is associated with other complications including vitreous hemorrhage and tractional retinal detachments. A common accompaniment of diabetic retinopathy is diabetic macular edema (DME) which is seen as a consequence of the disruption of the blood-retinal barrier (BRB) and subsequent fluid buildup within the macula ultimately culminating in loss of vision.

Therapeutics Development for Diabetic Retinopathy

Anti-Angiogenic Therapy
The introduction of anti-VEGF agents has changed the course of DR management, especially DME and PDR. Such drugs include ranibizumab, aflibercept, and bevacizumab which bind to and inhibit vascular endothelial growth factor (VEGF), resulting in decreased vascular permeability and neovascularization.
Anti-Inflammatory Therapy
Dexamehtasone and fluocinolone acetonide are examples of intravitreal corticosteroids that are effective in the management of recalcitrant DME. These drugs act by decreasing inflammation and vascular permeability which results in better macular edema and visual acuity.
Emerging Therapies
Neuroprotective agents, such as somatostatin or nerve growth factor, suppress neurodegeneration and emphasize on paralysis of retinal neurons. Pro-angiogenic factors including placental growth factor and erythropoietin are also under investigation to increase therapeutic effectiveness. Antioxidants such as alpha-lipoic acid or lutein, block oxidative stress, these are other factors that increase DR pathological changes.

Table 1. Therapeutics for diabetic retinopathy. (Wang W., et al., 2018)

Classification	Drugs	Status for DR Therapeutics	Clinical Benefits
Anti-VEGF	Pegaptanib (Macugen)	FDA approved	Greater BCVA improvement over sham groups in treating DME (phase 2/3, multicenter, two-year trial)
	Pegaptanib (Macugen)	FDA approved
	Aflibercept (EYLEA)	FDA approved	Greater BCVA improvement over laser in treating DME (VISTA, VIVID, DRCR.net Protocol T trials) and PDR (CLARITY trial)
Non-specific anti-angiogenic	Squalamine (inhibits VEGF and other growth factors)	Phase 2 trial (clinicaltrials.gov ID: NCT02349516) in progress	-
Non-specific anti-angiogenic	AKB-9778 (Tie2 activator)	Phase 2 trial (clinicaltrials.gov ID: NCT01702441) in progress	Greater reduction in CRT in the combination group over the ranibizumab monotherapy group (phase 2a clinical trial)
Intravitreal steroids	Triamcinolone	Off-label use	Greater improvements in triamcinolone + prompt laser group over laser alone in pseudophakic eyes
IL-6 inhibitor	EBI-031 (Section 3.2.2)	Clinical trial (clinicaltrials.gov ID: NCT02842541) in progress	-
Cardiolipin inhibitor	MTP-131 (OcuviaTM)	Clinical trial (clinicaltrials.gov ID: NCT02314299) in progress	-
Mitochondria specific antioxidant	ALA	Under clinical evaluation	Improved contrast sensitivity in type 1 and type 2 diabetes patients
Antioxidant	Lutein	Under clinical evaluation	Visual improvement in DR patients

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 develop cutting-edge solutions for the therapeutic of diabetic retinopathy. Our range of activities covers everything from diagnostics to the development of new therapies, all within an advanced technological and scientific framework.

Diagnostics Development

Karyotype Analysis Service
Omics Analysis Service
Biomarker Development Service
Artificial Intelligence Service
Customized Diagnostics Development

Therapeutic Development

Small Molecule Drug
Cell Therapy
Gene Therapy
Therapeutic Antibody
Therapeutic Peptide
Therapeutic Protein
Customized Therapy Development

Preclinical Research

Pharmacodynamics Study Services
Pharmacokinetics Study Services
Drug Safety Evaluation Services
Customized Research Services

Animal Models of Diabetic Retinopathy

Protheragen excels in developing sophisticated animal models that accurately replicate the pathophysiology of DR. Our animal models include:

Pharmacologically Induced Models

Alloxan-Induced Models
Streptozotocin (STZ)-Induced Models

Diet-Induced Models

High-Galactose Diet Models
High-Fat Diet Models

Genetic Models

Ins2Akita Mouse
Non-Obese Diabetic (NOD) Mouse
Leprdb Mouse
Zucker Diabetic Fatty (ZDF) Rat
Spontaneously Diabetic Torii (SDT) Rat

Environmental Exposure Models: Oxygen-Induced Retinopathy (OIR) Models

By leveraging our expertise in animal model development, Protheragen ensures that our clients have access to robust and relevant models for preclinical research. Our commitment to advancing DR therapeutics is reflected in our comprehensive suite of services, designed to support every stage of the development process. If you are interested in our services, please feel free to contact us.

References

Lechner, Judith, Olivia E. O'Leary, and Alan W. Stitt. "The pathology associated with diabetic retinopathy." Vision research 139 (2017): 7-14.
Wang, Wei, and Amy CY Lo. "Diabetic retinopathy: pathophysiology and treatments." International journal of molecular sciences 19.6 (2018): 1816.
Duh, Elia J., Jennifer K. Sun, and Alan W. Stitt. "Diabetic retinopathy: current understanding, mechanisms, and treatment strategies." JCI insight 2.14 (2017).