TIMP-1 affects the spatial distribution of dendritic processes of second-order neurons in a rat model of Retinitis Pigmentosa

Jung A. Shin, Yun Sung Eom, Wan Qing Yu, Norberto M. Grzywacz, Cheryl Mae Craft, Eun Jin Lee

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)41-52
Number of pages12
JournalExperimental Eye Research
Volume140
DOIs
StatePublished - 2015

Keywords

  • Bipolar cell
  • Cone mosaic
  • Cone outer segment
  • Horizontal cell
  • Retinitis pigmentosa
  • Synaptic protein
  • Tissue inhibitor of metalloproteinase-1(TIMP-1)

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