1. Volume 20, Issue 4, Pages 788-797 (April 2012)
Stanniocalcin-1 Rescued Photoreceptor Degeneration in Two Rat Models of Inherited Retinal Degeneration 
Gavin W Roddy, Robert H Rosa Jr, Joo Youn Oh, Joni H Ylostalo, Thomas J Bartosh, Hosoon Choi, Ryang Hwa Lee, Douglas Yasumura, Kelly Ahern, Gregory Nielsen, Michael T Matthes, Matthew M LaVail, Darwin J Prockop 
Molecular Therapy 
Volume 20, Issue 4, Pages (April 2012)
DOI: /mt
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

2. Figure 1
Intravitreal administration of stanniocalcin-1 (STC-1) rescued photoreceptors in the S334ter-3 rat. (a) Plot of outer nuclear layer (ONL) thickness taken from a total of 54 measurements in each retina (27 superior retina and 27 inferior retina) from a representative animal demonstrated that STC-1 injected twice significantly improved ONL thickness compared to uninjected (UI) controls. (b) Electroretinographic analysis performed at P19 following injection of STC-1 in the S334ter-3 rat at P9 (n = 10). Response amplitudes are from a stimulus intensity of 0.4 log cd sec/m2 in dark-adapted rats (scotopic b-wave) and light-adapted rats (photopic b-wave). Significant rescue of both scotopic and photopic b-waves was observed. (c,d) Light micrographs of the posterior retina of an S334ter-3 rat injected twice (at P9 and P12) with STC-1 and eyes taken at P19. The ONL in the treated eye (d) is approximately twice the thickness of that in the control eye (c), i.e., it contains approximately twice the number of photoreceptors. RPE, retinal pigment epithelium. Bar = 20 µm. *P < 0.05; **P < Error bars represent means ± SEM.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

3. Figure 2
Intravitreal administration of stanniocalcin-1 (STC-1) rescued photoreceptor gene expression in the S334ter-3 rat. Real time reverse transcription (RT)-PCR analysis for the photoreceptor genes. (a) Photoreceptor gene expression declined rapidly from P12–P14 in the untreated S334ter-3 rat. (b) Treatment with STC-1 rescued expression of four photoreceptor genes compared to uninjected (UI) control eyes from the same rats after one injection (1× STC-1) or two injections (2× STC-1). Eyes taken at P19. *P < 0.05; **P < Error bars represent means ± SEM.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

4. Figure 3
Intravitreal administration of stanniocalcin-1 (STC-1) rescued photoreceptors in the Royal College of Surgeons (RCS) rat. (a,b) Light micrographs of the posterior retina of an RCS rat injected twice (at P21 and P28) with STC-1 and eyes taken at P42. The outer nuclear layer (ONL) in the two eyes is similar in thickness. However, in the (a) uninjected control eye, a large percentage of photoreceptor nuclei are dead and pyknotic (arrowheads), and some are coalesced into large masses of chromatin (arrow), typical of RCS retinas at this age. In the (b) STC-1-treated eye, far fewer pyknotic nuclei are present and the rod outer segment debris zone is thicker than in the control eye. D, debris zone; RPE, retinal pigment epithelium; IS, photoreceptor inner segments. Bar = 20 µm. (c) Electroretinographic analysis performed at P42 following injections of STC-1 in the RCS rat at P21 and P42. Response amplitudes are from a stimulus intensity of 0.4 log cd sec/m2 in dark-adapted rats (scotopic b-wave). Significant rescue of the scotopic b-wave was observed. *P < Error bars represent means ± SEM.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

5. Figure 4
Intravitreal administration of stanniocalcin-1 (STC-1) rescued photoreceptor gene expression in the Royal College of Surgeons (RCS) rat. Real-time reverse transcription (RT)-PCR analysis for the photoreceptor genes. (a) Photoreceptor gene expression underwent a gradual decline in the untreated RCS rat between P21 and P45. The decline was more gradual than in the S334ter-3 rat (compare with Figure 2). (b) A single injection of STC-1 (1× STC-1) increased the levels of three of the photoreceptor transcripts. Two injections of STC-1 (2× STC-1) rescued expression of the four photoreceptor genes compared to vehicle controls. *P < 0.05; **P < Error bars represent means ± SEM.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

6. Figure 5
Intravitreal administration of stanniocalcin-1 (STC-1) increased UCP-2 gene expression and decreased levels of reactive oxygen species (ROS) products in the Royal College of Surgeons (RCS) rat. (a) Real time reverse transcription (RT)-PCR analysis for the mitochondrial uncoupling protein-2 (UCP-2) 3 days after injection of STC-1 at P21. (b,c) ELISA analysis for two markers of oxidative damage in the retina: protein carbonyl (b) and nitrotyrosine (c) content at P42 after injections of STC-1 at P21 and P28. *P < 0.05; **P < 0.01; ***P < Error bars represent means ± SEM.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions

7. Figure 6
Genes upregulated in both the S334ter-3 and Royal College of Surgeons (RCS) rat retinas following intravitreal administration of stanniocalcin-1 (STC-1). Heat maps of genes upregulated over 1.5-fold by STC-1 treatment in both models. STC-1-treated samples were compared with phosphate-buffered saline (PBS)-treated samples within each model. The S334ter-3 rats were injected with 1 µg of STC-1 on P9 and P12, and retinas were taken for assay on P19. The RCS rats were injected with 2.5 µg STC-1 on P21 and P28, and retinas were taken for assay on P42. The administration of STC-1 produced upregulation of a series of identical recovery-associated genes in both models.
Molecular Therapy  , DOI: ( /mt )
Copyright © 2012 The American Society of Gene & Cell Therapy Terms and Conditions