Postnatal hyperglycemia alters amino acid profile in retinas (model of Phase I ROP)
Jarrod C. Harman,
Aldina Pivodic,
Anders K. Nilsson,
Myriam Boeck,
Hitomi Yagi,
Katherine Neilsen,
Minji Ko,
Jay Yang,
Michael Kinter,
Ann Hellström,
Zhongjie Fu
Affiliations
Jarrod C. Harman
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Aldina Pivodic
The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Anders K. Nilsson
The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Myriam Boeck
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
Hitomi Yagi
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan
Katherine Neilsen
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Minji Ko
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Jay Yang
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Michael Kinter
Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
Ann Hellström
The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Zhongjie Fu
Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Corresponding author
Summary: Nutritional deprivation occurring in most preterm infants postnatally can induce hyperglycemia, a significant and independent risk factor for suppressing physiological retinal vascularization (Phase I retinopathy of prematurity (ROP)), leading to compensatory but pathological neovascularization. Amino acid supplementation reduces retinal neovascularization in mice. Little is known about amino acid contribution to Phase I ROP. In mice modeling hyperglycemia-associated Phase I ROP, we found significant changes in retinal amino acids (including most decreased L-leucine, L-isoleucine, and L-valine). Parenteral L-isoleucine suppressed physiological retinal vascularization. In premature infants, severe ROP was associated with a higher mean intake of parenteral versus enteral amino acids in the first two weeks of life after adjustment for treatment group, gestational age at birth, birth weight, and sex. The number of days with parenteral amino acids support independently predicted severe ROP. Further understanding and modulating amino acids may help improve nutritional intervention and prevent Phase I ROP.
