title: Bone marrow-CNS connections: implications in the pathogenesis of diabetic retinopathy.
abstract: Diabetic retinopathy is the fourth most common cause of blindness in adults. Current therapies, including anti-VEGF therapy, have partial efficacy in arresting the progression of proliferative diabetic retinopathy and diabetic macular edema. This review provides an overview of a novel, innovative approach to viewing diabetic retinopathy as the result of an inflammatory cycle that affects the bone marrow (BM) and the central and sympathetic nervous systems. Diabetes associated inflammation may be the result of BM neuropathy which skews haematopoiesis towards generation of increased inflammatory cells but also reduces production of endothelial progenitor cells responsible for maintaining healthy endothelial function and renewal. The resulting systemic inflammation further impacts the hypothalamus, promoting insulin resistance and diabetes, and initiates an inflammatory cascade that adversely impacts both macrovascular and microvascular complications, including diabetic retinopathy (DR). This review examines the idea of using anti-inflammatory agents that cross not only the blood-retinal barrier to enter the retina but also have the capability to target the central nervous system and cross the blood-brain barrier to reduce neuroinflammation. This neuroinflammation in key sympathetic centers serves to not only perpetuate BM pathology but promote insulin resistance which is characteristic of type 2 diabetic patients (T2D) but is also seen in T1D. A case series of morbidly obese T2D patients with retinopathy and neuropathy treated with minocycline, a well-tolerated antibiotic that crosses both the blood-retina and blood-brain barrier is presented. Our results indicates that minocycine shows promise for improving visual acuity, reducing pain from peripheral neuropathy, promoting weight loss and improving blood pressure control and we postulate that these observed beneficial effects are due to a reduction of chronic inflammation.
authors.affiliation: Clinical and Translational Science Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Yellowlees Douglas
authors.forename: Ashay D
authors.initials: AD
authors.lastname: Bhatwadekar
authors.forename: Sergio
authors.initials: S
authors.lastname: Li Calzi
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Shaw
authors.forename: Debra
authors.initials: D
authors.lastname: Carnegie
authors.forename: Sergio
authors.initials: S
authors.lastname: Caballero
authors.forename: Quihong
authors.initials: Q
authors.lastname: Li
authors.forename: Alan W
authors.initials: AW
authors.lastname: Stitt
authors.forename: Mohan K
authors.initials: MK
authors.lastname: Raizada
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001813:Blood-Retinal Barrier / Q000502:physiology; D001853:Bone Marrow / Q000294:innervation*; D002490:Central Nervous System / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000150:complications*; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000209:etiology*; D006801:Humans; D013564:Sympathetic Nervous System / Q000502:physiology; D014792:Visual Acuity / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents