Bhatwadekar A.D.,Eugene and Marilyn Glick Eye Institute |
Bhatwadekar A.D.,University of Florida |
Duan Y.,Eugene and Marilyn Glick Eye Institute |
Chakravarthy H.,Michigan State University |
And 4 more authors.
Stem Cells | Year: 2016
Ataxia telangiectasia mutated (ATM) acts as a defense against a variety of bone marrow (BM) stressors. We hypothesized that ATM loss in BM-hematopoietic stem cells (HSCs) would be detrimental to both HSC function and microvascular repair while sustained ATM would be beneficial in disease models of diabetes. Chronic diabetes represents a condition associated with HSC depletion and inadequate vascular repair. Gender mismatched chimeras of ATM-/- on wild type background were generated and a cohort were made diabetic using streptozotocin (STZ). HSCs from the STZ-ATM-/-chimeras showed (a) reduced self-renewal; (b) decreased long-term repopulation; (c) depletion from the primitive endosteal niche; (d) myeloid bias; and (e) accelerated diabetic retinopathy (DR). To further test the significance of ATM in hematopoiesis and diabetes, we performed microarrays on circulating angiogenic cells, CD34+ cells, obtained from a unique cohort of human subjects with long-standing (>40 years duration) poorly controlled diabetes that were free of DR. Pathway analysis of microarrays in these individuals revealed DNA repair and cell-cycle regulation as the top networks with marked upregulation of ATM mRNA compared with CD34+ cells from diabetics with DR. In conclusion, our study highlights using rodent models and human subjects, the critical role of ATM in microvascular repair in DR. © 2015 AlphaMed Press.
Guidoboni G.,Indiana University – Purdue University Indianapolis |
Guidoboni G.,Indiana University |
Harris A.,Eugene and Marilyn Glick Eye Institute |
Carichino L.,Indiana University – Purdue University Indianapolis |
And 2 more authors.
Mathematical Biosciences and Engineering | Year: 2014
Retinal hemodynamics plays a crucial role in the pathophysiology of several ocular diseases. There are clear evidences that the hemodynamics of the central retinal artery (CRA) is strongly affected by the level of intraocular pressure (IOP), which is the pressure inside the eye globe. However, the mechanisms through which this occurs are still elusive. The main goal of this paper is to develop a mathematical model that combines the mechanical action of IOP and the blood flow in the CRA to elucidate the mechanisms through which IOP elevation affects the CRA hemodynamics. Our model suggests that the development of radial compressive regions in the lamina cribrosa (a collagen structure in the optic nerve pierced by the CRA approximately in its center) might be responsible for the clinically-observed blood velocity reduction in the CRA following IOP elevation. The predictions of the mathematical model are in very good agreement with experimental and clinical data. Our model also identifies radius and thickness of the lamina cribrosa as major factors affecting the IOP-CRA relationship, suggesting that anatomical differences among individuals might lead to different hemodynamic responses to IOP elevation.
PubMed | Eugene and Marilyn Glick Eye Institute and Indiana University – Purdue University Indianapolis
Type: Journal Article | Journal: The British journal of ophthalmology | Year: 2014
Increased trans-lamina cribrosa pressure difference (TLCPD), the difference of intraocular pressure (IOP) and orbital cerebrospinal fluid pressure (CSF-P), has been investigated as a possible risk factor in glaucoma pathogenesis. In fact, lower CSF-P in the setting of normal IOP has been implicated as a potential risk factor for normal tension glaucoma. Increased TLCPD has been associated with decreased neuroretinal rim area and increased visual field defects. Furthermore, dysregulation of systemic blood pressure has been associated with changes in IOP. Recent studies have also suggested that increased body mass index (BMI) is associated with decreased prevalence of glaucoma, which may be due to an increased CSF-P with increased BMI found in many studies. Given the interaction of various pressures, their role in glaucoma pathophysiology has come under investigation and warrants further study in order to better understand the aetiology and progression of glaucoma.
Collinge J.E.,Eugene and Marilyn Glick Eye Institute |
Sprunger D.T.,Eugene and Marilyn Glick Eye Institute
Current Opinion in Ophthalmology | Year: 2013
PURPOSE OF REVIEW: Pediatric optic neuritis is an uncommon disorder with significant distinctions from its adult counterpart. Recognizing the features of this disorder and the potential association with progressive demyelinating processes is important for patients' evaluation and prognosis. RECENT FINDINGS: In the last few years, studies have expanded our understanding of demographic and presenting features for optic neuritis in the pediatric population. Emerging research on biomarkers and optical coherence tomography utility offers potential prognostic value in patient management. In addition, pooled research data have allowed for better understanding of the risks factors for progression from isolated optic neuritis to systemic demyelinating processes, such as multiple sclerosis. Although definitive evidence is lacking, corticosteroids remain the cornerstone of treatment. Various other immunosuppressive therapy studies have also reported success, particularly in refractory cases. SUMMARY: A comprehensive understanding of pediatric optic neuritis and its management remains elusive. A randomized clinical trial would potentially increase our knowledge and benefit the afflicted patients. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.