Journal
EXPERIMENTAL EYE RESEARCH
Volume 140, Issue -, Pages 41-52Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2015.08.005
Keywords
Retinitis pigmentosa; Tissue inhibitor of metalloproteinase-1 (TIMP-1); Cone mosaic; Bipolar cell; Horizontal cell; Synaptic protein; Cone outer segment
Categories
Funding
- VSoE Research Innovation Fund
- National Science Foundation [0310723]
- National Eye Institute [EY016093, EY11170, EY015851]
- NEI core grant (Doheny Eye Institute) [EY03040]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2014R1A6A3A03059828]
- Vision Research (Doheny Eye Institute)
- Div Of Engineering Education and Centers
- Directorate For Engineering [0310723] Funding Source: National Science Foundation
- National Research Foundation of Korea [2014R1A6A3A03059828] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. (C) 2015 Elsevier Ltd. All rights reserved.
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