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Dive into the research topics where Liliana P Paris is active.

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Featured researches published by Liliana P Paris.


Journal of Clinical Investigation | 2015

Neurovascular crosstalk between interneurons and capillaries is required for vision

Yoshihiko Usui; Peter D Westenskow; Toshihide Kurihara; Edith Aguilar; Susumu Sakimoto; Liliana P Paris; Carli M Wittgrove; Daniel Feitelberg; M. Friedlander; Stacey K. Moreno; Michael I. Dorrell; Martin Friedlander

Functional interactions between neurons, vasculature, and glia within neurovascular units are critical for maintenance of the retina and other CNS tissues. For example, the architecture of the neurosensory retina is a highly organized structure with alternating layers of neurons and blood vessels that match the metabolic demand of neuronal activity with an appropriate supply of oxygen within perfused blood. Here, using murine genetic models and cell ablation strategies, we have demonstrated that a subset of retinal interneurons, the amacrine and horizontal cells, form neurovascular units with capillaries in 2 of the 3 retinal vascular plexuses. Moreover, we determined that these cells are required for generating and maintaining the intraretinal vasculature through precise regulation of hypoxia-inducible and proangiogenic factors, and that amacrine and horizontal cell dysfunction induces alterations to the intraretinal vasculature and substantial visual deficits. These findings demonstrate that specific retinal interneurons and the intraretinal vasculature are highly interdependent, and loss of either or both elicits profound effects on photoreceptor survival and function.


eLife | 2016

Hypoxia-induced metabolic stress in retinal pigment epithelial cells is sufficient to induce photoreceptor degeneration

Toshihide Kurihara; Peter D Westenskow; Marin L. Gantner; Yoshihiko Usui; Andrew Schultz; Stephen Bravo; Edith Aguilar; Carli M Wittgrove; M. Friedlander; Liliana P Paris; Emily Y. Chew; Gary Siuzdak; Martin Friedlander

Photoreceptors are the most numerous and metabolically demanding cells in the retina. Their primary nutrient source is the choriocapillaris, and both the choriocapillaris and photoreceptors require trophic and functional support from retinal pigment epithelium (RPE) cells. Defects in RPE, photoreceptors, and the choriocapillaris are characteristic of age-related macular degeneration (AMD), a common vision-threatening disease. RPE dysfunction or death is a primary event in AMD, but the combination(s) of cellular stresses that affect the function and survival of RPE are incompletely understood. Here, using mouse models in which hypoxia can be genetically triggered in RPE, we show that hypoxia-induced metabolic stress alone leads to photoreceptor atrophy. Glucose and lipid metabolism are radically altered in hypoxic RPE cells; these changes impact nutrient availability for the sensory retina and promote progressive photoreceptor degeneration. Understanding the molecular pathways that control these responses may provide important clues about AMD pathogenesis and inform future therapies. DOI: http://dx.doi.org/10.7554/eLife.14319.001


Nature Communications | 2015

Comprehensive bioimaging with fluorinated nanoparticles using breathable liquids

Michael E. Kurczy; Zheng-Jiang Zhu; Julijana Ivanisevic; Adam M. Schuyler; Kush Lalwani; Antonio F. Santidrian; John David; Anand Giddabasappa; Amanda J. Roberts; Hernando J. Olivos; Peter J. O'Brien; Lauren Franco; Matthew W. Fields; Liliana P Paris; Martin Friedlander; Caroline H. Johnson; Adrian A. Epstein; Howard E. Gendelman; Malcolm R. Wood; Brunhilde H. Felding; Gary J. Patti; Mary E. Spilker; Gary Siuzdak

Fluorocarbons are lipophobic and non-polar molecules that exhibit remarkable biocompatibility, with applications in liquid ventilation and synthetic blood. The unique properties of these compounds have also enabled mass spectrometry imaging of tissues where the fluorocarbons act as a Teflon-like coating for nanostructured surfaces to assist in desorption/ionization. Here we report fluorinated gold nanoparticles (f-AuNPs) designed to facilitate nanostructure imaging mass spectrometry. Irradiation of f-AuNPs results in the release of the fluorocarbon ligands providing a driving force for analyte desorption. The f-AuNPs allow for the mass spectrometry analysis of both lipophilic and polar (central carbon) metabolites. An important property of AuNPs is that they also act as contrast agents for X-ray microtomography and electron microscopy, a feature we have exploited by infusing f-AuNPs into tissue via fluorocarbon liquids to facilitate multimodal (molecular and anatomical) imaging.


Stem Cells International | 2016

iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study

Peter D Westenskow; Felicitas Bucher; Stephen Bravo; Toshihide Kurihara; Daniel Feitelberg; Liliana P Paris; Edith Aguilar; Jonathan H. Lin; Martin Friedlander

Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE) viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes.


Annual Review of Vision Science | 2015

Angiogenesis and Eye Disease

Yoshihiko Usui; Peter D Westenskow; Salome Murinello; Michael I. Dorrell; Lea Scheppke; Felicitas Bucher; Susumu Sakimoto; Liliana P Paris; Edith Aguilar; Martin Friedlander

The retina consists of organized layers of photoreceptors, interneurons, glia, epithelial cells, and endothelial cells. The economic model of supply and demand used to appropriately determine cost is highly applicable to the retina, in which the extreme metabolic demands of phototransduction are met by precisely localized and designed vascular networks. Proper development and maintenance of these networks is critical to normal visual function; dysregulation is characteristic of several devastating human diseases, including but not limited to age-related macular degeneration and diabetic retinopathy. In this article, we focus on the lessons learned from the study of retinal vascular development and how these lessons can be used to better maintain adult vascular networks and prevent retinal diseases. We then outline the vasculotrophic contributions from neurons, retinal pigment epithelium (RPE) cells, and glia (specifically microglia) before we shift our focus to pathology to provide molecular contexts for neovascular retinal diseases. Finally, we conclude with a discussion that applies what we have learned about how retinal cells interact with the vasculature to identify and validate therapeutic approaches for neurovascular disease of the retina.


Journal of diabetes & metabolism | 2015

A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant

Liliana P Paris; Yoshihiko Usui; Josefina Serino; Joaquim Sá; Martin Friedlander

Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing.


International Ophthalmology | 2015

Parinaud’s syndrome due to an unilateral vascular ischemic lesion

Josefina Serino; João Martins; Liliana P Paris; Ana Duarte; Isabel Ribeiro

A 59-year-old man who complained of binocular vertical diplopia after an exploratory laparotomy, complicated by cardiorespiratory arrest during anesthetic induction, was found to have Collier’s sign, anisocoria, complete paralysis of upward vertical gaze associated with convergence-retraction nystagmus on attempted upgaze and skew deviation with hypertropia in the left eye without ptosis, and an absent Bielschowsky sign. Magnetic resonance imaging of the brain showed a small lesion in the left paramedian midbrain compatible with microvascular ischemic sequelae. This patient was diagnosed with Parinaud’s syndrome (dorsal midbrain syndrome) associated with a vertical strabismus from an unilateral vascular ischemic paramedian midbrain lesion.


Metabolomics | 2016

Global metabolomics reveals metabolic dysregulation in ischemic retinopathy

Liliana P Paris; Caroline H. Johnson; Edith Aguilar; Yoshihiko Usui; Kevin Cho; Lihn T. Hoang; Daniel Feitelberg; H. Paul Benton; Peter D Westenskow; Toshihide Kurihara; Jennifer K Trombley; Kinya Tsubota; Shunichiro Ueda; Yoshihiro Wakabayashi; Gary J. Patti; Julijana Ivanisevic; Gary Siuzdak; Martin Friedlander


Investigative Ophthalmology & Visual Science | 2017

Clinical features and a novel CHM mutation in a Portuguese family with X-linked choroideremia

Liliana P Paris; Márcia Rodrigues; Luísa Coutinho-Santos


Investigative Ophthalmology & Visual Science | 2016

β-catenin in retinal interneurons is important for maintaining stability of the retinal microvasculature

Yoshihiko Usui; Peter D Westenskow; Toshihide Kurihara; Edith Aguilar; Liliana P Paris; Susumu Sakimoto; Salome Murinello; Felicitas Bucher; Daniel Feitelberg; Martin Friedlander

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Edith Aguilar

Scripps Research Institute

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Daniel Feitelberg

Scripps Research Institute

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Carli M Wittgrove

Scripps Research Institute

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Yoshihiko Usui

Scripps Research Institute

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Stephen Bravo

Scripps Research Institute

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Felicitas Bucher

Scripps Research Institute

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Gary Siuzdak

Scripps Research Institute

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