Hari Jayaram

Oregon Health & Science University, Casey Eye Institute, Fulbright / Fight for Sight Scholar

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Medical University of Vienna

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Papers by Hari Jayaram

Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

by Hari Jayaram and Susan Downes

Journal of Medical Case Reports, 2008

Introduction: Refsum disease is a potentially lethal and disabling condition associated with reti... more

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Acquisition of RGC phenotype in human Müller glia with stem cell characteristics is accompanied by upregulation of functional nicotinic acetylcholine receptors

Molecular vision, 2013

Human Müller glia with stem cell characteristics (hMGSCs) can be induced to express genes and pro... more Human Müller glia with stem cell characteristics (hMGSCs) can be induced to express genes and proteins of retinal ganglion cells (RGCs) upon in vitro inhibition of Notch-1 activity. However, it is not known whether expression of these markers is accompanied by acquisition of RGC function. This study investigated whether hMGSCs that express RGC markers also display neural functionality, as measured by their intracellular calcium concentration ([Ca(2+)]i) responsiveness following neurotransmitter stimulation in vitro. Changes in mRNA expression of RGC markers and neurotransmitter receptors were assessed either by conventional or quantitative reverse transcription PCR (RT-PCR), while changes in protein levels were confirmed by immunocytochemistry. The [Ca(2+)]i levels were estimated by fluorescence microscopy. We showed that while undifferentiated hMGSCs displayed a profound elevation of [Ca(2+)]i after stimulation with N-methyl-D-aspartate (NMDA), this was lost following Notch-1 inhib...

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Transplantation of photoreceptors derived from human Muller glia restore rod function in the P23H rat

Stem cells translational medicine, 2014

Müller glia possess stem cell characteristics that have been recognized to be responsible for the... more Müller glia possess stem cell characteristics that have been recognized to be responsible for the regeneration of injured retina in fish and amphibians. Although these cells are present in the adult human eye, they are not known to regenerate human retina in vivo. Human Müller glia with stem cell characteristics (hMSCs) can acquire phenotypic and genotypic characteristics of rod photoreceptors in vitro, suggesting that they may have potential for use in transplantation strategies to treat human photoreceptor degenerations. Much work has been undertaken in rodents using various sources of allogeneic stem cells to restore photoreceptor function, but the effect of human Müller glia-derived photoreceptors in the restoration of rod photoreceptor function has not been investigated. This study aimed to differentiate hMSCs into photoreceptor cells by stimulation with growth and differentiation factors in vitro to upregulate gene and protein expression of CRX, NR2E3, and rhodopsin and variou...

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Stem Cell Based Therapies for Glaucoma

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Regulatory and Pathogenic Roles of Müller Glial Cells in Retinal Neovascular Processes and Their Potential for Retinal Regeneration

Frontiers in Diabetes, 2010

Abstract Mϋller glial cells are known to play a very important role in retinal homeostasis, and m... more

Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. St... more Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. Stem cell-based therapies offer hope for these patients at risk of or suffering from blindness due to the deterioration of the neural retina. Various sources of stem cells are currently being investigated, ranging from human embryonic stem cells to adult-derived induced pluripotent stem cells as well as human Müller stem cells, with the first clinical trials to investigate the safety and tolerability of human embryonic stem cell-derived retinal pigment epithelium cells having recently commenced. This review aims to summarize the latest advances in the development of stem cell strategies for the replacement of retinal neurons and their supportive cells, the retinal pigment epithelium (RPE) affected by retinal degenerative conditions. Particular emphasis will be given to the advances in stem cell transplantation and the challenges associated with their translation into clinical practice.

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Acta Ophthalmologica Scandinavica 2005

Optimized feline vitrectomy technique for therapeutic stem cell delivery to the inner retina

Veterinary Ophthalmology, 2014

Objective To describe an optimized surgical technique for feline vitrectomy which reduces bleedin... more Objective To describe an optimized surgical technique for feline vitrectomy which reduces bleeding and aids posterior gel clearance in order to facilitate stem cell delivery to the inner retina using cellular scaffolds. Procedures Three-port pars plana vitrectomies were performed in six-specific pathogen-free domestic cats using an optimized surgical technique to improve access and minimize severe intraoperative bleeding. Results The surgical procedure was successfully completed in all six animals. Lens sparing vitrectomy resulted in peripheral lens touch in one of three animals but without cataract formation. Transient bleeding from sclerotomies, which was readily controlled, was seen in two of the six animals. No cases of vitreous hemorrhage, severe postoperative inflammation, retinal detachment, or endophthalmitis were observed during postoperative follow-up. Conclusions Three-port pars plana vitrectomy can be performed successfully in the cat in a safe and controlled manner when the appropriate precautions are taken to minimize the risk of developing intraoperative hemorrhage. This technique may facilitate the use of feline models of inner retinal degeneration for the development of stem cell transplantation techniques using cellular scaffolds.

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Supratentorial and Infratentorial Intraparenchymal Hemorrhage Secondary to Intracranial CSF Hypotension Following Spinal Surgery

Spine, 2002

A single case study was conducted. To detail the occurrence of multiple intracranial, intraparenc... more A single case study was conducted. To detail the occurrence of multiple intracranial, intraparenchymal hemorrhages following an iatrogenic acute reduction in cerebral spinal fluid pressure following excision of an intradural extramedullary spinal tumor. Multiple supratentorial, intraparenchymal, intracranial hemorrhages following an acute reduction in cerebral spinal fluid pressure have not been previously reported in the literature. A case report and literature review are presented. The patient made an uneventful full recovery. Intracranial hemorrhage must be considered in the differential diagnosis of patients presenting with persistent headache following spinal surgery when the dura has been breached and is associated with significant cerebrospinal fluid loss.

Independent Adipogenic and Contractile Properties of Fibroblasts in Graves’ Orbitopathy: An In Vitro Model for the Evaluation of Treatments

PLoS ONE, 2014

Graves' orbitopathy (GO) is a disfiguring and sometimes blinding disease, characterised by inflam... more Graves' orbitopathy (GO) is a disfiguring and sometimes blinding disease, characterised by inflammation and swelling of orbital tissues, with fibrosis and adipogenesis being predominant features. Little is known about the disease aetiology and the molecular mechanisms driving the phenotypic changes in orbital fibroblasts are unknown. Using fibroblasts isolated from the orbital fat of undiseased individuals or GO patients, we have established a novel in vitro model to evaluate the dual profile of GO cells in a three-dimensional collagen matrix; this pseudo-physiological 3D environment allows measurement of their contractile and adipogenic properties. GO cells contracted collagen matrices more efficiently than control cells following serum or TGFb1 stimulation, and showed a slightly increased ability to proliferate in the 3D matrix, in accordance with a fibro-proliferative phenotype. GO cells, unlike controls, also spontaneously differentiated into adipocytes in 3D cultures -confirming an intrinsic adipogenic profile. However, both control and GO cells underwent adipogenesis when cultured under pathological pressure levels. We further demonstrate that a Thy-1-low population of GO cells underlies the adipogenic -but not the contractile -phenotype and, using inhibitors, confirm that the contractile and adipogenic phenotypes are regulated by separate pathways. In view of the current lack of suitable treatment for GO, we propose that this new model testing the duality of the GO phenotype could be useful as a preclinical evaluation for the efficacy of potential treatments.

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Spontaneous Globe Luxation Associated with Shallow Orbits and Floppy Eyelid Syndrome

Orbit, 2008

Spontaneous globe luxation is a rare and distressing phenomenon. We report three cases which char... more Spontaneous globe luxation is a rare and distressing phenomenon. We report three cases which characterise the aetiology of spontaneous anterior globe luxation in the presence of a shallow orbital configuration and lax eyelids. All patients suffered from floppy eyelid syndrome (FES). Orbital imaging revealed no orbital masses and normal extraocular muscles. Shallow orbits with significant globe projection was noted. There was no clinical, radiological or serological evidence of thyroid ophthalmopathy. In this group of patients, the aetiology of spontaneous globe luxation is likely to be contingent on both shallow orbits and lax eyelids. The different treatment options for this condition are considered.

Transient Monocular Blindness Successfully Treated by Lowering Intraocular Pressure

Neuro-Ophthalmology, 2008

We describe an elderly gentleman with a ten-year history of transient monocular blindness of the ... more

Concomitant primary breast carcinoma and primary choroidal melanoma: a case report

Journal of Medical Case Reports, 2008

Choroidal melanoma and choroidal metastasis are distinct pathological entities with very differen... more Choroidal melanoma and choroidal metastasis are distinct pathological entities with very different treatments and prognoses. They may be difficult to distinguish to the untrained observer. A case of concomitant choroidal melanoma in a woman with primary breast carcinoma is described. The choroidal lesion was thought initially to be a metastasis, and treated with external beam radiotherapy. The tumour did not regress but remained stable in size for a period of three years. Following referral to an ophthalmologist, the diagnosis was revised after re-evaluation of the clinical, ultrasonographic and angiographic findings. Although metastases are the most common ocular tumour, a differential diagnosis of a concurrent primary ocular malignancy should always be considered, even in patients with known malignant disease. Thorough ophthalmic evaluation is important, as multiple primary malignancies may occur concomitantly. The prognostic and therapeutic implications of accurate diagnosis by an ophthalmologist are of profound significance to affected patients and their families.

Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

Journal of Medical Case Reports, 2008

Introduction: Refsum disease is a potentially lethal and disabling condition associated with reti... more

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Objective measurement of intraocular lens movement and dioptric change with a focus shift accommodating intraocular lens

by David Spalton and Hari Jayaram

Journal of Cataract & Refractive Surgery, 2006

To objectively measure the shift and refractive change of the 1CU accommodating intraocular lens ... more To objectively measure the shift and refractive change of the 1CU accommodating intraocular lens (IOL) (HumanOptics) and compare them to that of a monofocal AcrySof MA30 IOL (Alcon Laboratories) in the fellow eye. Ophthalmology Department, St. Thomas&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; Hospital, London, United Kingdom. Thirty patients who had bilateral cataract surgery 18 to 24 months previously with a 1CU IOL prospectively randomly allocated to 1 eye and an AcrySof MA30 monofocal IOL to the other eye were examined. Distance correction, near vision, reading fluency, near point, and defocus to minus spheres were measured. Intraocular lens shift to an accommodative stimulus following instillation of pilocarpine 4% was measured with the ACMaster. Refractive change between distance and near was measured with the Tracey wavefront analyzer. Of the original 30 patients recruited, complete measurements could only be obtained for 20. There was no significant difference in near visual function with either IOL. A small anterior movement of the 1CU was seen with accommodation 0.010 mm +/- 0.028 (SD). After pilocarpine 4% instillation, a forward movement of 0.220 +/- 0.169 mm was seen with the 1CU compared to a backward movement of 0.028 +/- 0.095 with the MA30. There was no significant correlation between distance corrected near visual acuity and IOL movement. No change in spherical equivalent between distance and near was seen on wavefront analysis of either IOL. Small forward movement of the 1CU IOL was seen with accommodation and increased following pilocarpine, compared to the posterior movement of the MA30 IOL. The amount of the IOL shift was not sufficient to provide useful near vision, but the difference suggests that the engineering concept behind the 1CU IOL is valid.

Fellow-eye comparison of posterior capsule opacification with AcrySof SN60AT and AF-1 YA-60BB blue-blocking intraocular lenses

by David Spalton, Hari Jayaram, Georgia Cleary, and Mayank Nanavaty

Journal of Cataract & Refractive Surgery, 2008

PURPOSE: To compare posterior capsule opacification (PCO) between 2 microincision hydrophilic int... more

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Posterior capsule opacification after implantation of CeeOn Edge 911A, PhacoFlex SI-40NB, and AcrySof MA60BM lenses

Journal of Cataract & Refractive Surgery, 2004

To perform an intraindividual comparison of posterior capsule opacification (PCO) with 2 foldable... more To perform an intraindividual comparison of posterior capsule opacification (PCO) with 2 foldable intraocular lenses (IOLs) and a foldable acrylic IOL 1 year after in-the-bag implantation. Seven German ophthalmology centers. In an open prospective randomized multicenter study, each center intraindividually compared a high-refractive-index, sharp-edged optic silicone IOL (CeeOn Edge 911A, Pharmacia) with a high-refractive-index, round-edged optic silicone IOL (PhacoFlex SI-40NB, Allergan) or a sharp-edged optic acrylic IOL (AcrySof MA60BM, Alcon). Of 288 randomized patients, 247 had standard phacoemulsification with in-the-bag IOL implantation in both eyes by the same surgeon. One eye of each patient received a CeeOn Edge IOL and the fellow eye, an AcrySof or PhacoFlex IOL. A morphologic evaluation of PCO was performed using the Evaluation of Posterior Capsule Opacification (EPCO) system 1 to 2 weeks and 11 to 14 months after surgery. The digital pictures were evaluated by an independent investigator who was blind to the type of IOL. Intraindividual differences in EPCO scores were statistically evaluated by a 1-sided binomial test at an alpha-level of 5%. One year after surgery, 127 patients with the AcrySof IOL and 102 patients with the PhacoFlex IOL in the control eye were reexamined. Functional results, safety, and handling were not significantly different between the 3 IOLs. All reexamined eyes had a very low PCO grade. The EPCO values revealed less PCO in eyes with the CeeOn Edge IOL than in eyes with the AcrySof or PhacoFlex IOL, but the difference was not statistically significant. A neodymium:YAG laser capsulotomy was performed in 1 eye with a CeeOn Edge IOL, 1 eye with an AcrySof IOL, and 2 eyes with a PhacoFlex IOL. The EPCO PCO grade was low 1 year after implantation of CeeOn Edge 911A, PhacoFlex SI-40NB, and AcrySof MA60BM IOLs; there was no statistically significant difference between the IOLs. The impact of IOL material and edge design on PCO development might be relevant in a long-term follow-up of this study.

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Atopic rhinitis: a risk factor for spontaneous wound dehiscence following removal of a continuous penetrating keratoplasty suture

Graefe's Archive for Clinical and Experimental Ophthalmology, 2005

Dear Editor, We report a case of spontaneous wound dehiscence following removal of a continuous p... more

Adult retinal stem cells revisited

The open ophthalmology journal, 2010

Recent advances in retinal stem cell research have raised the possibility that these cells have t... more Recent advances in retinal stem cell research have raised the possibility that these cells have the potential to be used to repair or regenerate diseased retina. Various cell sources for replacement of retinal neurons have been identified, including embryonic stem cells, the adult ciliary epithelium, adult Müller stem cells and induced pluripotent stem cells (iPS). However, the true stem cell nature of the ciliary epithelium and its possible application in cell therapies has now been questioned, leaving other cell sources to be carefully examined as potential candidates for such therapies. The need for identification of the ontogenetic state of grafted stem cells in order to achieve their successful integration into the murine retina has been recognized. However, it is not known whether the same requirements may apply to achieve transplant cell integration into the adult human eye. In addition, the existence of natural barriers for stem cell transplantation, including microglial acc...

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$Research paper thumbnail of Refractory discoid lupus erythematosis of the eyelid successfully treated with intra-lesional triamcinolone$

Refractory discoid lupus erythematosis of the eyelid successfully treated with intra-lesional triamcinolone

Eye, 2008

management of retinal detachment. This patient's retinal detachment most closely related to scena... more management of retinal detachment. This patient's retinal detachment most closely related to scenario 4 in Ahmad's paper. 1 From the survey, 51-78% of respondents elected for surgical intervention, depending on the presence of a demarcation line. The management of these conditions is clearly controversial. The complication encountered here, although rare, is a cautionary tale and reminds us of the old adage primum non nocere.

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Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

by Hari Jayaram and Susan Downes

Journal of Medical Case Reports, 2008

Introduction: Refsum disease is a potentially lethal and disabling condition associated with reti... more

Download

Acquisition of RGC phenotype in human Müller glia with stem cell characteristics is accompanied by upregulation of functional nicotinic acetylcholine receptors

Molecular vision, 2013

Download

Transplantation of photoreceptors derived from human Muller glia restore rod function in the P23H rat

Stem cells translational medicine, 2014

Download

Stem Cell Based Therapies for Glaucoma

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Regulatory and Pathogenic Roles of Müller Glial Cells in Retinal Neovascular Processes and Their Potential for Retinal Regeneration

Frontiers in Diabetes, 2010

Abstract Mϋller glial cells are known to play a very important role in retinal homeostasis, and m... more

Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

Download

Acta Ophthalmologica Scandinavica 2005

Optimized feline vitrectomy technique for therapeutic stem cell delivery to the inner retina

Veterinary Ophthalmology, 2014

Download

Supratentorial and Infratentorial Intraparenchymal Hemorrhage Secondary to Intracranial CSF Hypotension Following Spinal Surgery

Spine, 2002

Independent Adipogenic and Contractile Properties of Fibroblasts in Graves’ Orbitopathy: An In Vitro Model for the Evaluation of Treatments

PLoS ONE, 2014

Download

Spontaneous Globe Luxation Associated with Shallow Orbits and Floppy Eyelid Syndrome

Orbit, 2008

Transient Monocular Blindness Successfully Treated by Lowering Intraocular Pressure

Neuro-Ophthalmology, 2008

We describe an elderly gentleman with a ten-year history of transient monocular blindness of the ... more

Concomitant primary breast carcinoma and primary choroidal melanoma: a case report

Journal of Medical Case Reports, 2008

Midlife diagnosis of Refsum Disease in siblings with Retinitis Pigmentosa – the footprint is the clue: a case report

Journal of Medical Case Reports, 2008

Introduction: Refsum disease is a potentially lethal and disabling condition associated with reti... more

Download

Objective measurement of intraocular lens movement and dioptric change with a focus shift accommodating intraocular lens

by David Spalton and Hari Jayaram

Journal of Cataract & Refractive Surgery, 2006

Fellow-eye comparison of posterior capsule opacification with AcrySof SN60AT and AF-1 YA-60BB blue-blocking intraocular lenses

by David Spalton, Hari Jayaram, Georgia Cleary, and Mayank Nanavaty

Journal of Cataract & Refractive Surgery, 2008

PURPOSE: To compare posterior capsule opacification (PCO) between 2 microincision hydrophilic int... more

Download

Posterior capsule opacification after implantation of CeeOn Edge 911A, PhacoFlex SI-40NB, and AcrySof MA60BM lenses

Journal of Cataract & Refractive Surgery, 2004

Download

Atopic rhinitis: a risk factor for spontaneous wound dehiscence following removal of a continuous penetrating keratoplasty suture

Graefe's Archive for Clinical and Experimental Ophthalmology, 2005

Dear Editor, We report a case of spontaneous wound dehiscence following removal of a continuous p... more

Adult retinal stem cells revisited

The open ophthalmology journal, 2010

Download

$Research paper thumbnail of Refractory discoid lupus erythematosis of the eyelid successfully treated with intra-lesional triamcinolone$

Refractory discoid lupus erythematosis of the eyelid successfully treated with intra-lesional triamcinolone

Eye, 2008

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