FORM 2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENT RULES , 2003 PROVISIONAL SPECIFICATION (See Section 10; rule 13) INHIBITION OF VEGF-A SECRETION, ANGIOGENESIS AND/OR NEO ANGIOGENESIS BY siNA MEDIATED KNOCKDOWN OF VEGF-C AND RHOA RELIANCE LIFE SCIENCES PVT.LTD an Indian Company having its Registered Office at Dhirubhai Ambani Life Sciences Centre, R-282, TTC A reaofMIDC, Thane Belapur Road, Rabale, Navi Mumbai - 400 701 Maharashtra India. FIELD OF THE INVENTION: The present invention relates to use of short nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules, for modulating gene and protein expression, including compounds, compositions and synergistic combination of small nucleic acid molecules that modulate RhoA and/or VEGF-C gene expression. The compounds and methods of the present invention have applications in modulating VEGF-A expression and secretion, angiogenesis and/or neoangiogenesis, either alone or in combination with other therapies. BACKGROUND OF THE INVENTION Angiogenesis is the formation of new blood vessels or enlargement of existing vessels. In the human body, there exists both pro-angiogenie (e.g., VEGF, bFGF, ANG-1) and anti-angiogenic (e.g., Angiostatin, Endostatin, and ANG-2) factors that help maintain homeostasis. Physiological or environmental insults can result in altering the proper balance of such factors, resulting in disease. Angiogenesis is required for many physiological and pathological processes, such as embryonic development, wound healing, tumor growth and metastasis, rheumatoid arthritis, diabetic retinopathy, atherosclerosis; and revascularization of ischemic myocardium, hind limb muscles, and brain. Lymphangiogenesis is critically important for tumor spread via the lymphatic system. The processes of blood and lymphatic angiogenesis are tightly regulated by several key angiogenic factors. These factors, which include FGF (fibroblast growth factor), VEGF (vascular endothelial growth factor), PDGF (platelet-derived growth factor), and angiopoietin families, modulate both blood and lymphatic vessel growth. Thus, blood and lymphatic angiogenesis are coordinately controlled by mitogens with overlapping functions. It is not clear how these factors selectively activate separate pathways of lymphatic or blood angiogenesis when both types of vessels are formed simultaneously. Although many molecular details of blood angiogenesis are known, the closely associated lymphatic system has remained poorly characterized due to the lack of specific molecular markers. During the last decade, however, a number of molecules unique to the lymphatic -2- vessels have been identified. With these tools, the lymphatic system and its relevance to disease can be analyzed at a molecular level. Among the known angiogenic factors, VEGF (VEGF-A) was previously thought to act only on blood vessels. However, a recent study reports that VEGF promotes lymphangiogenesis as well. In contrast to the VEGF family, the FGF family is known to have broader biological functions on a variety of cell types. Although the two FGF prototypes, FGF-1 and FGF-2, are potent angiogenic factors in vivo, the physiological and pathological relevance of these factors in regulation of angiogenesis needs to be established, particularly because both of them lack a classical signal sequence for secretion. The VEGF family includes at least five structurally related proteins, VEGF-A, VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (P1GF). These molecules interact with a set of cell surface receptors, VEGFR-1, VEGFR-2, and VEGFR-3, that show varying specificity and function. VEGF-C and VEGF-D bind to both VEGFR-2 and VEGFR-3 and promote formation of blood andlymph vessels. VEGF-B and P1GF bind to VEGFR-1 and modulate the effects of VEGF-A, but their roles in stimulation of angiogenesis remain controversial. In addition to its ability to stimulate angiogenesis, VEGF-A acts as a potent vascular permeability factor (VPF). A large body of work indicates that VEGFR-2 is the receptor that mediates VEGF-A-induced angiogenic and permeability effects. In support of this notion, VEGF-B and P1GF, which only interact with VEGFR-1, lack angiogenic and vascular permeability activity. Thickness of the endothelial cell layer in capillaries is induced by the three growth factors (VEGF-A-GAAUUAGGCUGUAACUACUUUAUdAdA-3' (SEQ IDNO:17) 5>-UUAUAAAGUAGUUACAGCCUAAUUCAC-3' (SEQ ID NO:18) * Scrambled RINA used as negative control = "negative RINA" in this and other experiments presented below. The scrambled "negative" RINA is a commercially available negative control from Ambion Inc. EXAMPLE 3: VEGF-C and RhoA expression analysis by reverse transcriptase PCR HUVEC (Human Umblical Vascular Endothelial Cells, ATCC) and PC3 (Prostate cancer cells, ATCC) cell lines were cultured in 5% C02 at 37°C following instructions from ATCC. Cells at 60-70% confluence were subjected to total RNA isolation followed by first strand cDNA preparation using Qiagen Fast lane cell cDNA kit with minor modifications. Briefly 20,000 cells were pelleted and washed once with buffer FCW. Cells were lysed for 15 min. at room temperature using buffer FCP. Genomic DNA contamination was eliminated by the addition of gDNA wipeout buffer by incubating at 42.5°C for 30 min. First strand cDNA was synthesized by the addition of Quantiscript reverse transcriptase at 42.5°C for 45 min. followed by incubation at 95°C for 3 min. The first strand cDNA prepared was either used immediately for reverse transcriptase PCR or stored unu'i farther use at -20°C. First strand cDNA were amplified by PCR using the following primer sequences: VEGF-C Forward Primer: 5'-AAAGAACCTGCCCCAGAAAT-3' (SEQIDNO:19) VEGF-C Reverse Primer: 5!-TGGTGGTGGAACTTCTTTCC-3' (SEQIDNO:20) VEGF-C Probe: 5'- 6-FAM-AATCCTGGAAAATGTGCCTG-3' (SEQIDNO:21) RhoA Forward Primer: 5'-TATCGAGGTGGATGGAAAGC-3' (SEQ ID NO:22) RhoA Reverse Primer: 5'-TTCTGGGGTCCACTTTTCTG-3' (SEQ ID NO:23) -34- RhoA Probe: 5'- 6-FAM-CCATCGACAGCCCTGATAGT-3' (SEQIDNO:24) Amplified products were resolved over 2% agarose. Arrowheads in Figure 1 indicate amplicon of specific gene products obtained, showing that HUVEC and PC3 cells express both VEGF-C and RhoA. See lanes 1 (PC3 VEGF-C), 3 (PC3 RhoA), 6 (HUVEC VEGF-C) and 8 (HUVEC RhoA). EXAMPLE 4: Oligonucleotide transfections/siRNA transfections HUVEC cells (human umbilical vascular endothelial cells), HeLa (cervical cancer), PC-3 (prostate cancer), HTB-38 (colorectal carcinoma) and ARPE-19 (normal diploid retinal pigmented epithelial cells) cell lines were obtained from ATCC and were maintained at 70-80% confluence with change of medium 24 h prior to transfection in T-25 flasks. Cell lines were used for all transfections of siRNA before reaching passage number ten unless otherwise mentioned. At the time of transfection, cells were trypsinized and reseeded into either a 24-well plate or any other standard tissue culture disposable plasticware at appropriate cell density. Unless otherwise stated, all transfections were carried-out in a 24-well plate with varying cell densities depending on cell lines used for a given experiment. Each well of a 24-well plate is seeded with appropriate cell densities one hour prior to transfections with growth medium not exceeding 400 uL and incubated in a 37°C incubator with 5% CO2. To this medium, diluted siRNA were added to a final concentration of lOnM (in 97uL of Opti-MEM I added 0.3uL of siRNA from a 20uM stock). To the diluted siRNA, 3 uL of Hiperfect transfection agent (Qiagen) was added and mixed by vortexing before incubating at room temperature for 10 min. For combination of siRNAs, such as VEGF-C and RhoA siRNAs, individual siRNA were mixed lOnM each and used. All experiments also included a negative control siRNA obtained from Ambion. All siRNA and transfection mixes were performed as master mixes from which appropriate volumes were added to the wells seeded with cells. At the end of incubation, siRNA-liposome complexes were mixed thoroughly and gently added dropwise to each well. The wells of 24-well plate were mixed to uniformity by gently rocking the plate back and forth as well as sideways. The plates were incubated for appropriate incubation -35- times in 37°C CO2 incubators for further analysis of cells. Transfection efficiencies are obtained for each cell line by counting number of celis showing Cy3-labeled siRNA (using negative control siRNA from Ambion) after 16 h of transfection. After 16 h of transfection, cells were trypsinised and washed once in PBS and suspended in the same. Cells that were suspended in PBS were observed with an inverted fluorescent microscope and were counted for the number of fluorescent labeled cells and total number of cells in 15 different fields of microscope each field. The percentage of cells that were labeled with Cy3 siRNA was determined and thus transfection efficiency was derived. Of all the cell lines tested, HeLa gave 97% transfection efficiency, where as ARPE-19 gave only 85 % efficiency, as shown in Table 3. Table 3. Percent of Transfection efficiencies as determined by Cy3 labeled siRNA for different cell lines. Cell line transfected % of Transfection HUVEC 95±6.0 HeLa 97±5.0 PC3 85±3.0 ARPE-19 85±5.0 HTB-38 90±9.0 EXAMPLE 5: VEGF-C and RhoA siRNAs inhibit VEGF-A secretion A) Inhibitory effect of VEGF-C and RhoA on VEGF-A secretion: PC3 (prostate cancer), ARPE-19 (retinal pigmented epithelial cells), HeLa (cervical cancer) and HCC-38 (breast cancer) cells were transfected with 10 nM siRNA, i.e., one of six siRNAs (RINA 6, 17, 30 against VEGF-C, and RINA 50, 51, 52 against RhoA), using HiPerFect Transfection Reagent following protocol of manufacturer (Qiagen). At the end of 72 h of transfection cell, supernatants were analyzed by Sandwich ELISA as per the instructions of VEGF-A ELISA kit (Calbiochem). A standard curve was obtained for concentrations (15.6 pg/mL to 1000 pg/mL) as shown in Figure 2. -36- The quantity of secreted VEGF-A in supematants was estimated from the standard curve for VEGF-A (Figure 2). See Table 4 below. All tested VEGF-C siRNAs (RINA 6, 17 and RINA 30) caused inhibition of VEGF-A secretion in two or more cell lines (PC3, ARPE-19 and/or HeLa) upon transfection. Of the three VEGF-C siRNAs tested, RINA 30 transfection of HeLa cells showed the greatest effect. RINA 30 inhibited secretion of VEGF-A by 68% in HeLa, as compared to mock (negative RINA) treated cells. Table 4. Knockdown of VEGF-C inhibits VEGF-A secretion (165) (soluble form of VEGF-A secreted in supernatant, as detected by ELISA) VEGF-A secreted in pg/mL* siRNA PC3 ARPE-19 HeLa RINA 6 842.76±0.28 714.76±0.85 435.33±0.15* RINA 17 918.6±0.96 453.43±0.01* NA RINA 30 775.76±0.13* 386.6±0.15* 300±0.89* Negative RINA 1187.1±0.75 705.6±0.48 949.01±0.67 Untreated 1452.16±10 952.4±21.3 1103.11±11 * Indicates P<0.05 in comparison with negative RINA Similarly, all tested RhoA siRNAs (RINA 50, 51 and RINA 52) caused inhibition of VEGF-A secretion in at least one cell line (ARPE-19, HeLa and/or HCC-38) upon transfection. Of the three RhoA siRNAs tested, RINA 50 showed the greatest effect. RINA 50 inhibited secretion of VEGF-A by 40% in HeLa cells, as compared to mock treated cells. RINA 52 inhibited secretion of VEGF-A by 27% in ARPE-19 cells. Table 5. Knockdown of RhoA inhibits VEGF-A secretion VEGF-A secreted in pg/mL* siRNA ARPE-19 HeLa HCC-38 RINA 50 712±3.5 657±4.5* 388±4.5* RINA 51 938±2.8 N.A N.A -37- RINA 52 687±6.3* N.A N.A Negative RINA 930±6.8 1103±1.23 470±6.2 Untreated 938±5.2 1391±0.24 466±2.0 * Indicates P<0.05 in comparison with negative RINA Results presented herein indicate that siRNAs directed to either VEGF-C or RhoA unexpectedly inhibit expression and secretion of VEGF-A. The results likewise indicate for the first time that inhibition of either VEGF-C or RhoA expression leads to an inhibition of VEGF-A expression, secretion and VEGF-A-specific cell signaling. Results will indicate that use of a VEGF-C siRNA and a Rho siRNA together will inhibit VEGF-A expression and secretion in a synergistic manner, as compared to additive effects of using VEGF-C siRNA or RhoA siRNA alone B) Quantitative Real time PCR analysis of decrease in expression levels of target gene CRhoA and VEGF-C) mRNA: The expression levels of VEGF-C and RhoA genes were determined by Real time PCR. The cell lines used in this study included PC3 (prostate cancer) HeLa (cervical cancer), ARPE-19 (retinal pigmented epithelial cells) and HTB-38 (colorectal cancer) obtained from ATCC. Cells were transfected either with RINA 52 or RINA 30 and negative control siRNA. At the end of 72 h of post transfection, the first strand cDNA preparation was carried-out using Qiagen Fast lane cell cDNA kit with minor modifications. Briefly 20,000 cells were pelleted and washed once with buffer FCW. Cells were lysed for 15 min at room temperature using buffer FCP. Genomic DNA contamination was eliminated by the addition of gDNA wipeout buffer by incubating at 42.5°C for 30min. First strand cDNA was synthesized by the addition of Quantiscript reverse transcriptase at 42.5°C for 45 min followed by incubation at 95°C for 3 min. The first strand cDNA prepared was either used immediately for quantitative Real time PCR or stored till further use at -20°C. Real time quantitative PCR can be accomplished following standard protocols and using commercially available machines such as ABI 7800, 7400 or 7900. -38- First strand cDNA from antisense, negative siRNA and untreated samples were used as template and quantified the levels of mRNA by normalizing against the internal control (3-actin. The expression of RhoA and VEGF-C was determined as a percent decrease in expression level over untreated cells as indicated in Table 6. Table 6: Percent decrease in expression levels of target gene at 72 h post transfection as determined by Real Time PCR* Cell-line RhoA Negative RINA Untreated HeLa 96.50 -1.0 0 HTB-38 96.30 NA 0 PC3 73.82 6.0 0 VEGF-C ARPE-10 85.0 5.0 0 PC3 87.0 NA 0 Quantitative real time PCR analysis of RINA 52 transfected cells shows a 96% decrease in mRNA levels of RhoA gene in HeLa and HTB-38 cells, as compared to mock transfected cells. RINA 30 transfection resulted in a decrease in mRNA levels of gene VEGF-C by 87% and 85% respectively in the case of PC3 and ARPE-19 cells. C) Determination of Inhibitory Concentration 50 (IC50) values for RTNA 30 transfected MCF-7 cells for VEGF-C and VEGF-A by Sandwich ELISA: Breast cancer cell lines (MCF-7) were transfected with varying concentration of VEGF-C RINA 30 (0.01, 0.1, 1.0, 10.0, and 100.0 nM) or with negative RINA. At the end of 72 h of transfection, cell culture supernatants were clarified from respective wells and subjected to Sandwich ELISA to determine the level inhibitory levels for VEGF-C cell expression, as well as VEGF-A expression. VEGF ELISA kit,Human,Cat.no QIA51,CALBIOCHEM for VEGF-A and Quantikine VEGF-C ,Human, kit R&D systems,Cat.no;DVEC00 for VEGF-C. With regard to VEGF-C expression (as compared negative RINA transfected cells), RINA 30 reached a plateau of IC70 at 10 nM -39- concentration, and exhibited an IC50 value of 0.8 nM, as shown in Figure 3A. VEGF-A reached a plateau of IC48 at 10 nM concentration of RINA 30, while its IC50 value remained at 0.8 nM, as shown in the Figure 3B. The IC50 values and Real time PCR data show that RINA 30 is highly potent and works to inhibit VEGF-C and VEGF-A expressions at concentrations as low as 0.8 nM. Results presented herein show that expression of VEGF-C regulates expression levels of VEGF-A, indicating that there exists a homeostasis and that both VEGF-C and VEGF-A are required for neoangiogenesis. D) Analysis of VEGF-C protein levels by Western blot Cells (Hela, PC3, MCF-7, HTb-38, ARPE-19 and HUVEC) are transfected with RINA 6, 17 and 30. At the end of 72 h of transfection, protein lysates are obtained employing Mammalian protein extraction reagent, MPER (Pierce) and are subjected to Western blot analysis. The protein knockdown levels are detected from the analysis of protein blots. VEGF-C expression levels will be inhibited in the cells upon transfection with RINA 6, 17 and/or 30, as compared to negative RINA transfected cells. E) Analysis of RhoA protein levels by Western blot: Cells (Hela, PC3, MCF-7, HTb-38, ARPE-19 and HUVEC) are transfected with RINA 50, 51 and 52. At the end of 72 h of transfection, protein lysates are obtained employing Mammalian protein extraction reagent, MPER (Pierce) and are subjected to Western blot analysis. The protein knockdown levels are detected from the analysis of protein blots. RhoA expression levels will be inhibited in the cells upon transfection with RINA 50, 51 and/or 52, as compared to negative RINA transfected cells. EXAMPLE 6: Knockdown of RhoA inhibits phosphorylation of ROCK Rho Kinase 1 (ROCK-1) and Rho kinase 2 (ROCK-2) are effector molecules of RhoA. ROCK-1 and ROCK-2 are Ser/Thr kinases that are activated by RhoA, resulting in cytoskeleta! reorganization. This reorganization results in endothelial cell morphogenesis leading to formation of new blood vessels. -40- Knockdown of RhoA and its effect on activation of Rho kinases was determined. Cells (ARPE-19) were transfected with RINA 50, 51 or 52 and analyzed for protein expression or phosphorylation status of ROCK-1 or ROCK-2 at the end of 72 h of transfection (Figure 4A and 4B). Protein lysates were made using mammalian protein extraction reagent (MPER, Calbiochem) following manufactures protocol. Based on Bradford total protein estimations, equal quantities of proteins were resolved over 10% SDS PAGE. Proteins resolved over the SDS-PAGE were subjected to Western blot transfer at 110 V for 70 min. on to a pre-wet nitrocellulose membrane along with pre-stained rainbow molecular weight markers (Amersham Biosciences). The transfer of proteins by electro-blotting was confirmed by Ponceau S staining (Sigma). The blot was incubated in blocking solution (5% skim milk powder) for 1 h at room temperature on a rocking platform. Before incubating with an anti-ROCK-1 mouse monoclonal IgGl (Santa Cruz) or an anti-phospho-ROCK-2 antibody ABCAM ab 24843 and mouse alpha tubulin antibody (Sigma) as internal control, the blot was washed over an orbital shaker for 5 min each with change of PBST (phosphate buffered saline containing 0.1% Tween 20). The blot was incubated with primary antibody overnight at 4°C. After washing with PBST to remove any non-specific bound primary antibodies, the blots were incubated with secondary antibodies conjugated with alkaline phosphatase for two hours at room temperature over an orbital shaker. Secondary antibodies included rabbit anti-mouse antibody conjugated with alkaline phosphatase (Sigma) to detect tubulin and Rock-1, goat anti-rabbit antibody (SIGMA) to detect ROCK-2 phospho-antibody. Antibodies used are as;Figure 4A Primary antibodies 1.Rabbit anti phospho rho kinase alpha(Rock-2) antibody, Abeam, Cat.no. ab24 843.2, Mouse Anti alpha Tubulin Antibody,SIGMA,Cat.no. T6199.Secondariy antibodies are 1. rabbit anti-mouse antibody(gamma chain specific) conjugated with alkaline phosphatase (Sigma,Cat.no.A3438)2.Goat anti Rabbit antibody(Whole molecule) conjugated with alkaline phosphatase (SIGMA Cat no A3687).and for Figure 4B Primary antibodies l.Anti ROCK-1 mouse monoclonal IgGl(Santacruz Cat no,SC17794.2.Mouse Anti alpha Tubulin Antibody,SIGMA,Cat.no. T6199.Secondariy antibodies are 1. rabbit anti-mouse antibody(gamma chain specific) conjugated with alkaline phosphatase (Sigma,Cat.no.A3438). Blots were washed three times with PBST for 10 min each before -41- being developed with BCIP/NAT substrate solution (Sigma). Protein bands corresponding to phosphorylated ROCK-2 (160 KDa) and tubulin (51 Kda) as endogenous control were detected, as shown in the Figure 4A. Protein bands corresponding to ROCK-1 (160 KDa) and tubulin (51 Kda) as endogenous control were detected, as shown in the Figure 4B. RINA 52 caused the greatest inhibition of ROCK-2 phosphorylation among the three siRNAs (RINA 50, 51 and 52) tested in this experiment. See lane 3 in Figure 4A. The results presented here show for the first time that siRNAs directed to RhoA inhibit ROCK phosphorylation (as demonstrated for ROCK-2 here) in relevant cells, such as retinal pigmented epithelial cells. Thus, siRNAs of the present invention inhibit the ROCK signaling pathway, without affecting expression of ROCK itself. This is in contrast to results expected when using a siRNA directed to ROCK itself, which presumably affects gene expression of ROCK. EXAMPLE 7: RINA 30 and RINA 52 do not induce an interferon response upon transfection for ARPE-19 cells Retinal pigmented cells were transfected with 10 nM siRNA, i.e., VEGF-C siRNA (RINA 6 and 30) and RhoA siRNA (RINA 50, 51 and 52). At the end of 20 h of transfection, cells were lysed and total RNA was prepared. Interferon response pathway specific gene expression was determined for the following genes following manufacturers instructions of Interferon Response Detection Kit for validation of siRNA experiments (SBI): Interferon response genes OAS1(NM_016816) and OAS2 (NM__016817.1) represents 2\5'-oligoadenylate synthetase (OAS); MXl (NM_002462.2) Myxovirus (Influenza virus) resistance protein family; IFITM1 (NM_003641.2) interferon inducible trans-membrane proteins. Of the siRNAs tested, RINA 30 and 52 caused only a low level enhancement of expression with regard to genes MXl or ISGF3y, respectively, and caused little to no measurable enhancement of expression of other genes involved in eliciting an interferon response. See Table 7. Thus, results presented herein demonstrate that cellular responses observed upon transfection with siRNAs of the present invention, such as VEGF-C siRNA 30 and RhoA siRNA 52, are not due to an activation of an -42- interferon response, but rather are due to inhibition of expression of the specific gene(s) of interest. Table 7. Lack of interferon response induced by RINA 30 and 52, as seen in reverse transcriptase PCR analysis ARPE-19 Interferon response as determined by RT-PCR Gene UT 6 30 50 51 52 OAS1 -f + + ++ + + OAS2 + + + + + + ISGF3y + ++ + -H-+ +++ ++ MX1 + ++ ++ +++ + + NOTE: UT = Untreated + Indicates levels in untransfected . ++ Indicates observable enhancement. +-H- Indicates prominent unambiguous enhancement. EXAMPLE 8: In vitro angiogenesis assay Human umbilical vein endothelial cells (HUVEC) obtained from ATCC were cultured in endothelial cell culture medium following directions from ATCC. HUVEC cells were transfected individually with 5 nM of RINA 6, 30, 50, 52 and negative siRNA. At the end of 48 h of transfection, cells were trypsinized and plated on ECM (extracellular matrix) coated wells of a 96-well plate in triplicate, each at a concentration of 5000 cells per well. Cells seeded onto ECM coated 96-well plates were cultured and observations were made under light microscope for the following parameters to be quantified at the end of 8 h of incubation on the ECM: A) Migration of HUVEC cells to close proximity of each other B) Alignment of cells in the form of a vessel or tube C) Formation of vascular sprouts -43- D) Establishment of closed polygons form E) Formation of complex mesh like structures. Comparisons were made between untreated, negative siRNA treated and RINA treated wells in duplicate for each. The number of sprouts or vessels present in each well was quantified at five different fields from duplicates. Results herein show that HUVEC cells transfection with VEGF-C or RhoA siRNA caused an inhibition of the formation of vessels, as compared to that seen in mock or untreated cells. Of all siRNAs tested, RINA 30 and 52 exhibited maximum inhibition of the vessels formation. In addition, no vessel formation was noted even after 16 h after plating on ECM in cells transfected with both VEGF-C RINA 30 and RhoA RINA 52. These results indicate that knockdown of either RhoA or VEGF-C inhibits vessel formation, as shown in Figure 5 and Table 8. Table 8. Percent of angiogenesis inhibition as obtained from light microscopic observations post 8 h of incubation on extracellular matrix (ECM) RINA % of Angiogenesis Std 6 13.04 ±2.0 30 0* ±0.0 50 13.04* ±1.2 52 6.52* ±3.0 30X52 0* ±0.0 Negative siRNA 80.10 ±10.0 UT 100 ±7.5 * Indicates P<0.05 in comparison with negative RINA Using varying amounts of the RTNAs disclosed above, experiments will demonstrate that the combination of a VEGF-C RINA and a RhoA RINA of the present invention inhibits angiogenesis and neoangiogenesis in a synergistic manner, as compared to an additive effect, i.e., using a VEGF-C RINA alone + using a RhoA RINA alone. -44- EXAMPLE 9: Effect of knockdown of VEGF-C and RhoA on cytokine profile in ARPE-19 cells Retinal pigmented epithelial cells are transfected with RINA 30, 52 or their combination. At the end of 72 h of transfection, cell supernatants are obtained from the RINA treated, negative siRNA treated and untreated cells. The supernatants are analyzed for 28 different cytokines following the protocol of Human Cytokine Array Panel A Array kit from R&D systems. The implications of change in expression profiles of various cytokines in relation to angiogenesis will be obtained. Most of the pro-angiogeneic cytokines will be inhibited to various degrees, while anti-angiogenic cytokines may be over-expressed. EXAMPLE 10: Transcriptome analysis of VEGF-C and RhoA knockdown in retinal pigmented epithelial cells To test the specificity of the different VEGF-C and RhoA siRNAs, retinal pigmented epithelial cells (ARPE-19) are transfected with RINA 30, 52 or their combination as described earlier. At the end of 72 h of transfection, total RNA is prepared following the protocol of Qiagen total RNA isolation kit (RNeasy Mini kit). Total RNA of 2ug is suspended in lOuL of water. The quality of RNA is checked on denaturing formaldehyde gels and OD ratio is determined using Perkin Elmer Spectrophotometer. One jag of total RNA is converted into DIG labeled cRNA following the protocol of Nano In-vitro Transcription amplification kit from Applied Biosystems. Fourteen micrograms of cRNA is hybridized to Human Genome Survey arrays containing 60 base pair probes for interrogation of 29,098 genes. The arrays are hybridized at 55°C for 17 h and subsequently washed and bound to antibody against DIG coupled with alkaline phosphatase. After the addition of chemiluminescent detection substrate, the arrays are scanned on the 1700 analyzer. Autogridding are performed by the imaging software and the result file is created that transforms the intensity of each gene into a numeric value, -45- i.e., a higher the signal corresponds to a higher the numeric value, which corresponds to a higher amount of gene present in the sample. Controls are added for each and every step of the assay starting from reverse transcription (RT), in vitro transcription (IVT), hybridization and chemiluminescence detection. A quality report is generated for these controls that help to ascertain the success of the microarray experiment. A secondary analysis using Spotfire will then be performed. The Spotfire software normalizes the data and performs a "t test" to determine the differentially expressed genes between two conditions. It also averages the replicates and determines a fold change value for the two conditions. The probe IDs that are differentially expressed are sorted through bead studio 3.0 version of software and change in expression profile of various genes above 3 fold is obtained. Analysis of the change in gene expression profiles and their relevance to inhibition of angiogenesis process will be obtained. All of the compositions and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of certain embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the methods described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents that are chemically or physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims. Dated this 21st day of November, 2008 For Reliance Life Sciences Pvt Ltd K. VrSubramaniam President