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1. Machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery

Author

Hsueh, Henry T., Chou, Renee Ti, Rai, Usha, Liyanage, Wathsala, Kim, Yoo Chun, Appell, Matthew B., Pejavar, Jahnavi, Leo, Kirby T., Davison, Charlotte, Kolodziejski, Patricia, Mozzer, Ann, Kwon, HyeYoung, Sista, Maanasa, Anders, Nicole M., Hemingway, Avelina, Rompicharla, Sri Vishnu Kiran, Edwards, Malia, Pitha, Ian, Hanes, Justin, Cummings, Michael P., and Ensign, Laura M.

Published
2023
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11. Clinicopathologic Findings in Three Siblings With Geographic Atrophy

Author

Edwards, Malia M., primary, McLeod, D. Scott, additional, Shen, Mengxi, additional, Grebe, Rhonda, additional, Sunness, Janet S., additional, Bhutto, Imran A., additional, McDonnell, Erin, additional, Pado, Alexandra M., additional, Gregori, Giovanni, additional, Rosenfeld, Philip J., additional, and Lutty, Gerard A., additional

Published
2023
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12. Supplementary materials for machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery

Author

Chou, Renee Ti, Cummings, Michael P., Ensign, Laura M., Chou, Renee Ti, Hsueh, Henry T., Rai, Usha, Liyanage, Wathsala, Kim, Yoo Chun, Appell, Matthew B., Pejavar, Jahnavi, Leo, Kirby T., Davison, Charlotte, Kolodziejski, Patricia, Mozzer, Ann, Kwon, HyeYoung, Sista, Maanasa, Anders, Nicole M., Hemingway, Avelina, Rompicharla, Sri Vishnu Kiran, Edwards, Malia, Pitha, Ian, Hanes, Justin, Chou, Renee Ti, Cummings, Michael P., Ensign, Laura M., Chou, Renee Ti, Hsueh, Henry T., Rai, Usha, Liyanage, Wathsala, Kim, Yoo Chun, Appell, Matthew B., Pejavar, Jahnavi, Leo, Kirby T., Davison, Charlotte, Kolodziejski, Patricia, Mozzer, Ann, Kwon, HyeYoung, Sista, Maanasa, Anders, Nicole M., Hemingway, Avelina, Rompicharla, Sri Vishnu Kiran, Edwards, Malia, Pitha, Ian, and Hanes, Justin

Abstract

Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We developed a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) was conjugated to brimonidine, an intraocular pressure (IOP)-lowering drug that is prescribed for three times per day topical dosing, IOP reduction was observed for up to 18 days after a single intracameral HR97-brimonidine injection in rabbits. Further, the cumulative IOP-lowering effect was increased ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.

Published
2023

13. Internal limiting membrane disruption facilitates engraftment of transplanted human stem cell derived retinal ganglion cells

Author

Aguzzi, Erika A, primary, Zhang, Kevin Y, additional, Nagalingam, Arumugam, additional, Quillen, Sarah, additional, Hariharakumar, Shreya, additional, Chetla, Nitin, additional, Madhoun, Salaheddine, additional, Edwards, Malia M, additional, Quigley, Harry A, additional, Zack, Donald J, additional, and Johnson, Thomas V, additional

Published
2022
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25. A role for mast cells in geographic atrophy

Author

Ogura, Shuntaro, primary, Baldeosingh, Rajkumar, additional, Bhutto, Imran A., additional, Kambhampati, Siva P., additional, Scott McLeod, Donald, additional, Edwards, Malia M., additional, Rais, Rana, additional, Schubert, William, additional, and Lutty, Gerard A., additional

Published
2020
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39. Increased L ipocalin‐2 in the retinal pigment epithelium of Cryba1 c KO mice is associated with a chronic inflammatory response

Author

Valapala, Mallika, primary, Edwards, Malia, additional, Hose, Stacey, additional, Grebe, Rhonda, additional, Bhutto, Imran A., additional, Cano, Marisol, additional, Berger, Thorsten, additional, Mak, Tak W., additional, Wawrousek, Eric, additional, Handa, James T., additional, Lutty, Gerard A., additional, Samuel Zigler, J., additional, and Sinha, Debasish, additional

Published
2014
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44. Photoreceptor Degeneration, Azoospermia, Leukoencephalopathy, and Abnormal RPE Cell Function in Mice Expressing an Early Stop Mutation inCLCN2

Author

Edwards, Malia M., primary, de Evsikova, Caralina Marín, additional, Collin, Gayle B., additional, Gifford, Elaine, additional, Wu, Jiang, additional, Hicks, Wanda L., additional, Whiting, Carrie, additional, Varvel, Nicholas H., additional, Maphis, Nicole, additional, Lamb, Bruce T., additional, Naggert, Jürgen K., additional, Nishina, Patsy M., additional, and Peachey, Neal S., additional

Published
2010
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45. Mutations of the Opsin Gene (Y102H and I307N) Lead to Light-induced Degeneration of Photoreceptors and Constitutive Activation of Phototransduction in Mice

Author

Budzynski, Ewa, primary, Gross, Alecia K., additional, McAlear, Suzanne D., additional, Peachey, Neal S., additional, Shukla, Meera, additional, He, Feng, additional, Edwards, Malia, additional, Won, Jungyeon, additional, Hicks, Wanda L., additional, Wensel, Theodore G., additional, Naggert, Jurgen K., additional, and Nishina, Patsy M., additional

Published
2010
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46. Mutations in Lama1 Disrupt Retinal Vascular Development and Inner Limiting Membrane Formation

Author

Edwards, Malia M., primary, Mammadova-Bach, Elmina, additional, Alpy, Fabien, additional, Klein, Annick, additional, Hicks, Wanda L., additional, Roux, Michel, additional, Simon-Assmann, Patricia, additional, Smith, Richard S., additional, Orend, Gertraud, additional, Wu, Jiang, additional, Peachey, Neal S., additional, Naggert, Jürgen K., additional, Lefebvre, Olivier, additional, and Nishina, Patsy M., additional

Published
2010
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47. Increased Lipocalin-2 in the retinal pigment epithelium of Cryba1 c KO mice is associated with a chronic inflammatory response.

Author

Valapala, Mallika, Edwards, Malia, Hose, Stacey, Grebe, Rhonda, Bhutto, Imran A., Cano, Marisol, Berger, Thorsten, Mak, Tak W., Wawrousek, Eric, Handa, James T., Lutty, Gerard A., Samuel Zigler, J., and Sinha, Debasish

Subjects
*LIPOCALINS, *RHODOPSIN, *EPITHELIAL cells, *INFLAMMATION, *RETINAL degeneration, *GENE knockout, *LABORATORY mice
Abstract

Although chronic inflammation is believed to contribute to the pathology of age-related macular degeneration ( AMD), knowledge regarding the events that elicit the change from para-inflammation to chronic inflammation in the pathogenesis of AMD is lacking. We propose here that lipocalin-2 ( LCN2), a mammalian innate immunity protein that is trafficked to the lysosomes, may contribute to this process. It accumulates significantly with age in retinal pigment epithelial ( RPE) cells of Cryba1 conditional knockout ( cKO) mice, but not in control mice. We have recently shown that these mice, which lack βA3/A1-crystallin specifically in RPE, have defective lysosomal clearance. The age-related increase in LCN2 in the cKO mice is accompanied by increases in chemokine ( C- C motif) ligand 2 ( CCL2), reactive gliosis, and immune cell infiltration. LCN2 may contribute to induction of a chronic inflammatory response in this mouse model with AMD-like pathology. [ABSTRACT FROM AUTHOR]

Published
2014
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48. Genetic Modifiers That Affect Phenotypic Expression of Retinal Diseases.

Author

Tombran-Tink, Joyce, Barnstable, Colin J., Edwards, Malia M., Maddox, Dennis M., Won, Jungyeon, Naggert, Jürgen K., and Nishina, Patsy M.

Abstract

Variability in onset, progression, severity, and phenotypic expression is commonly observed in many retinal diseases (Tables 1 and 2). Although interfamily variability may be caused by environmental or allelic differences, intrafamily variability, when a common mutation is segregating, may also be due to genetic modifiers (1-3). In contrast to independently acting alleles that may lead to an additive effect on disease severity or age of onset, genetic modifiers are defined as background genes that epistatically interact with a given disease genotype to affect phenotypic outcome. In general, allelic variability at modifier loci does not in itself produce a phenotype. A single gene or possibly a combination of genes in the same or parallel pathways as the mutant gene may act to create a final effect on the expression of the disease phenotype. These modifiers may enhance the effect of the mutation to cause a more severe mutant phenotype or an earlier onset, or conversely, delay or reduce the mutant phenotype even to the extent of completely restoring the wild-type (WT) condition. [ABSTRACT FROM AUTHOR]

Published
2007
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49. VEGF 165b in the developing vasculatures of the fetal human eye.

Author

Baba, Takayuki, McLeod, D. Scott, Edwards, Malia M., Merges, Carol, Sen, Tanusree, Sinha, Debasish, and Lutty, Gerard A.

Abstract

VEGF165b is an anti-angiogenic form of VEGF165 produced by alternative splicing. The localization of pro-angiogenic VEGF165 and anti-angiogenic VEGF165b was investigated during development of the vasculatures in fetal human eyes from 7 to 21 weeks gestation (WG). The fetal vasculature of vitreous, which includes tunica vasculosa lentis (TVL), had moderate VEGF165 immunoreactivity at 7WG and very little VEGF165b. Both forms were elevated at 12WG. VEGF165 then decreased around 17WG when the TVL regresses but VEGF165b remained elevated. In choroid, VEGF165 was present in forming choriocapillaris (CC) and retinal pigment epithelium (RPE) at 7WG while VEGF165b was present in CC and mesenchymal precursors within the choroidal stroma. By 21WG, both forms were elevated in RPE and choroidal blood vessels but VEGF165b was apical and VEGF165 basal in RPE. Diffuse VEGF165 immunoreactivity was prominent in 12WG innermost retina where blood vessels will form while VEGF165b was present in most CXCR4+ progenitors in the inner neuroblastic layer and migrating angioblasts in the putative nerve fiber layer. By 21WG, VEGF165 was present in nerve fibers and VEGF165b in the inner Muller cell process. The localization of VEGF165b was distinctly different from VEGF165 both spatially and temporally and it was often associated with nucleus in progenitors. Developmental Dynamics 241:595-607, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2012
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50. how embarrassing!

Author

Kaplan, Debbie, Tristan, Kelly, Sternard, Wendy, Gager, Amber, Clarke, Beverly, Edwards, Malia, and Nelson, Mandy

Subjects
ANECDOTES, CHILDREN
Abstract

This section presents a variety of anecdotes about children. The 4-year-old daughter and 2-year-old son of Wendy Sternard yelling at each other in the playroom of a child-care center. Joshua, the 3-year-old son of Malia Edwards, replying to a question on what his baby brother eats. The 3-year-old son of Mandy Nelson on what his father does for a living.

Published
2007

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