Publications

2018

Lee A, Karamichos D, Onochie O, Hutcheon A, Rich C, Zieske J, Trinkaus-Randall V. Hypoxia modulates the development of a corneal stromal matrix model. Exp Eye Res. 2018;170:127–137.
Deposition of matrix proteins during development and repair is critical to the transparency of the cornea. While many cells respond to a hypoxic state that can occur in a tumor, the cornea is exposed to hypoxia during development prior to eyelid opening and during the diurnal sleep cycle where oxygen levels can drop from 21% to 8%. In this study, we used 2 three-dimensional (3-D) models to examine how stromal cells respond to periods of acute hypoxic states. The first model, a stromal construct model, is a 3-D stroma-like construct that consists of human corneal fibroblasts (HCFs) stimulated by a stable form of ascorbate for 1, 2, and 4 weeks to self-assemble their own extracellular matrix. The second model, a corneal organ culture model, is a corneal wound-healing model, which consists of wounded adult rat corneas that were removed and placed in culture to heal. Both models were exposed to either normoxic or hypoxic conditions for varying time periods, and the expression and/or localization of matrix proteins was assessed. No significant changes were detected in Type V collagen, which is associated with Type I collagen fibrils; however, significant changes were detected in the expression of both the small leucine-rich repeating proteoglycans and the larger heparan sulfate proteoglycan, perlecan. Also, hypoxia decreased both the number of Cuprolinic blue-positive glycosaminoglycan chains along collagen fibrils and Sulfatase 1, which modulates the effect of heparan sulfate by removing the 6-O-sulfate groups. In the stromal construct model, alterations were seen in fibronectin, similar to those that occur in development and after injury. These changes in fibronectin after injury were accompanied by changes in proteoglycans. Together these findings indicate that acute hypoxic changes alter the physiology of the cornea, and these models will allow us to manipulate the conditions in the extracellular environment in order to study corneal development and trauma.
PURPOSE: To report a simple, highly effective technique of simultaneous transconjunctival repair of upper and lower eyelid retraction in patients with thyroid eye disease (TED). METHODS: A retrospective interventional case review was conducted on 22 eyes of 19 TED patients. The lower eyelid was recessed with placement of a tarsoconjunctival spacer graft harvested from the upper eyelid. The upper eyelid was then recessed through the conjunctival incision used to harvest the tarsal graft. A temporary tarsorrhaphy was placed for 5-7 days. The postoperative outcome was assessed by measuring the margin reflex distance of the upper eyelid (MRD1), inferior scleral show (ISS), and lagophthalmos. RESULTS: The absolute change in MRD1 ranged from 0 to 5 mm with an average of 1.86 ± 1.34 mm. The absolute change in ISS ranged from 0 to 2 mm with an average of 1.3 ± 0.49 mm. One patient had postoperative lagophthalmos and 17 of 19 had improvement in their ocular surface exposure symptoms. None of the patients' grafts were observed to undergo absorption during the postoperative course. CONCLUSIONS: This technique of harvesting a free tarsoconjunctival graft from the upper eyelid as a posterior spacer for the lower while simultaneously recessing the upper eyelid through the same incision is an effective and durable method of correcting eyelid retraction in TED.
Maurer A, Pacouret S, Cepeda Diaz AK, Blake J, Andres-Mateos E, Vandenberghe L. The Assembly-Activating Protein Promotes Stability and Interactions between AAV’s Viral Proteins to Nucleate Capsid Assembly. Cell Rep. 2018;23(6):1817–1830.
The adeno-associated virus (AAV) vector is a preferred delivery platform for in vivo gene therapy. Natural and engineered variations of the AAV capsid affect a plurality of phenotypes relevant to gene therapy, including vector production and host tropism. Fundamental to these aspects is the mechanism of AAV capsid assembly. Here, the role of the viral co-factor assembly-activating protein (AAP) was evaluated in 12 naturally occurring AAVs and 9 putative ancestral capsid intermediates. The results demonstrate increased capsid protein stability and VP-VP interactions in the presence of AAP. The capsid's dependence on AAP can be partly overcome by strengthening interactions between monomers within the assembly, as illustrated by the transfer of a minimal motif defined by a phenotype-to-phylogeny mapping method. These findings suggest that the emergence of AAP within the Dependovirus genus relaxes structural constraints on AAV assembly in favor of increasing the degrees of freedom for the capsid to evolve.
McDermott A, Baidouri H, Woodward A, Kam W, Liu Y, Chen X, Ziemanski J, Vistisen K, Hazlett L, Nichols K, Argüeso P, Sullivan D. Short Tandem Repeat (STR) Profiles of Commonly Used Human Ocular Surface Cell Lines. Curr Eye Res. 2018;43(9):1097–1101.
PURPOSE: The purpose of this study is to establish the short tandem repeat (STR) profiles of several human cell lines commonly used in ocular surface research. MATERIALS AND METHODS: Independently DNA was extracted from multiple passages of three human corneal epithelial cell lines, two human conjunctival epithelial cell lines and one meibomian gland cell line, from different laboratories actively involved in ocular surface research. The samples were then subjected to STR analysis on a fee-for-service basis in an academic setting and the data compared against that in available databases. RESULTS: The STR profiles for the human corneal epithelial cells were different among the three cell lines studied and for each line the profiles were identical across the samples provided by three laboratories. Profiles for the human conjunctival epithelial cells were different among the two cell lines studied. Profiles for the meibomian gland cell line were identical across the samples provided by three laboratories. No samples were contaminated by elements of other cell lines such as HeLa. CONCLUSIONS: This comprehensive study provides verification of STR profiles for commonly used human ocular surface cell lines that can now be used as a reference by others in the field to authenticate the cell lines in use in their own laboratories.
Nowak-Sliwinska P, Alitalo K, Allen E, Anisimov A, Aplin A, Auerbach R, Augustin H, Bates D, Beijnum J, Bender H, Bergers G, Bikfalvi A, Bischoff J, Böck B, Brooks P, Bussolino F, Cakir B, Carmeliet P, Castranova D, Cimpean A, Cleaver O, Coukos G, Davis G, De Palma M, Dimberg A, Dings R, Djonov V, Dudley A, Dufton N, Fendt SM, Ferrara N, Fruttiger M, Fukumura D, Ghesquière B, Gong Y, Griffin R, Harris A, Hughes C, Hultgren N, Iruela-Arispe L, Irving M, Jain R, Kalluri R, Kalucka J, Kerbel R, Kitajewski J, Klaassen I, Kleinmann H, Koolwijk P, Kuczynski E, Kwak B, Marien K, Melero-Martin J, Munn L, Nicosia R, Noel A, Nurro J, Olsson AK, Petrova T, Pietras K, Pili R, Pollard J, Post M, Quax P, Rabinovich G, Raica M, Randi A, Ribatti D, Ruegg C, Schlingemann R, Schulte-Merker S, Smith L, Song J, Stacker S, Stalin J, Stratman A, Van de Velde M, Hinsbergh V, Vermeulen P, Waltenberger J, Weinstein B, Xin H, Yetkin-Arik B, Yla-Herttuala S, Yoder M, Griffioen A. Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis. 2018;
The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
Reshef E, Wolkow N, Jakobiec F, Yoon M. Histopathologic Findings of Linear Scleroderma Displaying Focal Trichiasis Secondary to Tarsal Thinning. Ophthalmic Plast Reconstr Surg. 2018;34(4):e124-e127.
Linear scleroderma en coup de sabre with ophthalmic findings has been previously described in the literature on numerous occasions. A 57-year-old woman presented with focal trichiasis secondary to tarsal thinning, adjacent to a linear brow and forehead deformity consistent with linear scleroderma en coup de sabre. Cases of linear scleroderma en coup de sabre involving the eyelids have been reported, most often with madarosis, ptosis, or skin atrophy; however, to the authors' knowledge, this is the first reported case of linear scleroderma associated with trichiasis and involvement of the deeper eyelid tissues, particularly the tarsus.
Rinaldi L, Merabet L, Vecchi T, Cattaneo Z. The spatial representation of number, time, and serial order following sensory deprivation: A systematic review. Neurosci Biobehav Rev. 2018;90:371–380.
The spatial representation of numerical and temporal information is thought to be rooted in our multisensory experiences. Accordingly, we may expect visual or auditory deprivation to affect the way we represent numerical magnitude and time spatially. Here, we systematically review recent findings on how blind and deaf individuals represent abstract concepts such as magnitude and time (e.g., past/future, serial order of events) in a spatial format. Interestingly, available evidence suggests that sensory deprivation does not prevent the spatial "re-mapping" of abstract information, but differences compared to normally sighted and hearing individuals may emerge depending on the specific dimension considered (i.e., numerical magnitude, time as past/future, serial order). Herein we discuss how the study of sensory deprived populations may shed light on the specific, and possibly distinct, mechanisms subserving the spatial representation of these concepts. Furthermore, we pinpoint unresolved issues that need to be addressed by future studies to grasp a full understanding of the spatial representation of abstract information associated with visual and auditory deprivation.
PURPOSE: Vision loss from age-related macular degeneration (AMD) has a profound effect on vision-related quality of life (VRQoL). The pupose of this study is to identify clinical factors associated with VRQoL using the Rasch- calibrated NEI VFQ-25 scales in bilateral advanced AMD patients. METHODS: We retrospectively reviewed 47 patients (mean age 83.2 years) with bilateral advanced AMD. Clinical assessment included age, gender, type of AMD, high contrast visual acuity (VA), history of medical conditions, contrast sensitivity (CS), central visual field loss, report of Charles Bonnet Syndrome, current treatment for AMD and Rasch-calibrated NEI VFQ-25 visual function and socioemotional function scales. The NEI VFQ visual function scale includes items of general vision, peripheral vision, distance vision and near vision-related activity while the socioemotional function scale includes items of vision related-social functioning, role difficulties, dependency, and mental health. Multiple regression analysis (structural regression model) was performed using fixed item parameters obtained from the one-parameter item response theory model. RESULTS: Multivariate analysis showed that high contrast VA and CS were two factors influencing VRQoL visual function scale (β = -0.25, 95% CI-0.37 to -0.12, p<0.001 and β = 0.35, 95% CI 0.25 to 0.46, p<0.001) and socioemontional functioning scale (β = -0.2, 95% CI -0.37 to -0.03, p = 0.023, and β = 0.3, 95% CI 0.18 to 0.43, p = 0.001). Central visual field loss was not assoicated with either VRQoL visual or socioemontional functioning scale (β = -0.08, 95% CI-0.28 to 0.12,p = 0.44 and β = -0.09, 95% CI -0.03 to 0.16, p = 0.50, respectively). CONCLUSION: In patients with vision impairment secondary to bilateral advanced AMD, high contrast VA and CS are two important factors affecting VRQoL.
Sié A, Diarra A, Millogo O, Zongo A, Lebas E, Bärnighausen T, Chodosh J, Porco T, Deiner M, Lietman T, Keenan J, Oldenburg C. Seasonal and Temporal Trends in Childhood Conjunctivitis in Burkina Faso. Am J Trop Med Hyg. 2018;
Acute conjunctivitis follows a seasonal pattern. Although its clinical course is typically self-limited, conjunctivitis epidemics incur a substantial economic burden because of missed school and work days. This study investigated seasonal and temporal trends of childhood conjunctivitis in the entire country of Burkina Faso from 2013 to 2016, using routine monthly surveillance from 2,444 government health facilities. A total of 783,314 cases were reported over the 4-year period. Conjunctivitis followed a seasonal pattern throughout the country, with a peak in April. A nationwide conjunctivitis outbreak with a peak in September 2016 was noted ( < 0.001), with an excess number of cases first detected in June 2016. Nationwide passive surveillance was able to detect an epidemic 3 months before its peak, which may aide in allocation of resources for containment and mitigation of transmission in future outbreaks.