TIMP-1 affects the spatial distribution of dendritic processes of second-order neurons in a rat model of Retinitis Pigmentosa.
Retinitis Pigmentosa (RP) is an inherited disorder that may lead to blindness. In the rhodopsin S334ter-line-3 rat model of RP, the death of rods induces spatial rearrangement of cones into regular ring mosaics. Using this model, we discovered that the ring mosaics are restored to a homogeneous distribution upon application of tissue inhibitor of metalloproteinase-1 (TIMP-1). In this study, we further investigated the cone migration and spatial distribution of second-order neurons and their connections to cones in the presence or absence of TIMP-1 using immunohistochemistry to identify retinal neurons and their connections with cones. M-opsin cell bodies and their outer segments were evaluated to determine whether TIMP-1 delays the degeneration of outer segments of cones. We observed that during cone rearrangement into ring mosaics in RP retina, dendritic processes of second-order neurons undergo remodeling to maintain their synaptic connections with the cones in the rings. TIMP-1 treatment induced the cones to rearrange and dendritic processes of second-order neurons to return to a more homogeneous spatial distribution. In addition, TIMP-1 treatment protected the outer segments of cones at later stages of retinal degeneration. Our findings clearly demonstrate that despite their dramatic spatial rearrangement, cones and second-order neuron processes maintain their synaptic connections before and after TIMP-1 treatment.
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Keck School of Medicine of the University of Southern California, USA; Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USA; Department of Anatomy, School of Medicine, Ewha Womans University, Seoul 158-710, South Korea.
Jung-A
JA
Shin
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Keck School of Medicine of the University of Southern California, USA; Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA.
Yun Sung
YS
Eom
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA.
Wan-Qing
WQ
Yu
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA; Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA, USA; University of Southern California Viterbi School of Engineering, Los Angeles, CA, USA; Department of Neuroscience, Georgetown University, Washington D.C, USA; Department of Physics, Georgetown University, Washington D.C, USA.
Norberto M
NM
Grzywacz
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Keck School of Medicine of the University of Southern California, USA; Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USA; Department of Cell & Neurobiology, Keck School of Medicine of the University of Southern California, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA.
Cheryl Mae
CM
Craft
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Keck School of Medicine of the University of Southern California, USA; Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USA; Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. Electronic address: eunjinl@usc.edu.
Eun-Jin
EJ
Lee
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement; D003712:Dendrites / Q000378:metabolism*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D058449:Intravitreal Injections; D008297:Male; D018613:Microscopy, Confocal; D009473:Neuronal Plasticity / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051245:Retinal Bipolar Cells / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000008:administration & dosage / Q000494:pharmacology*
D015415:Biomarkers; D005136:Eye Proteins; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1
Bipolar cell; Cone mosaic; Cone outer segment; Horizontal cell; Retinitis pigmentosa; Synaptic protein; Tissue inhibitor of metalloproteinase-1(TIMP-1)